The DOI matches its Crossref record; 139 of the 139 references it cites were found in a registry or an index; 78 of the 141 sources its claims cite were checked for support.
Fetal hemoglobin in sickle cell anemia
Open accessAbstract
Abstract Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease. This review focuses on (1) HbF quantitative trait loci and the geography of β-globin gene haplotypes, especially those found in the Middle East; (2) how HbF might differentially impact the pathophysiology and many subphenotypes of sickle cell disease; (3) clinical implications of person-to-person variation in the distribution of HbF among HbF-containing erythrocytes; and (4) reactivation of HbF gene expression using both pharmacologic and cell-based therapeutic approaches. A confluence of detailed understanding of the molecular basis of HbF gene expression, coupled with the ability to precisely target by genomic editing most areas of the genome, is producing important preliminary therapeutic results that could provide new options for cell-based therapeutics with curative intent.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
34 Partly supported · 31 No basis given · 25 No full text of the sources · 19 Supported · 11 Own interpretation · 8 Sources not found · 7 Supported so far · 5 Not supported · 1 Couldn’t confirm · 1 Not checked yet · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“An intronic SNP (rs35685045) in ANTXR1 (TEM8; chr2p13) was associated with HbF in 4 cohorts of adult AI haplotype patients.41,42”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Disputedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Results section identifies rs35685045 as an intronic ANTXR1 SNP associated with HbF, but it does not support association in four AI-haplotype cohorts. The Results report association in the Saudi AI cohorts and explicitly state that it was not found in the Indian AI cohort. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [42] Al-Ali, 2018, ANTXR1 intronic variants are associated with fetal hemoglobin in the Arab-Indian haplotype of sickle cell disease, Acta Haematol source
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Therefore, even when started early in life, the HbF response to hydroxyurea might wane.88”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Disputedcites [88] Hankins, 2014, From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia, Medicine (Baltimore) sourceExperimental — accuracy not yet measured
The Results section reports that HbF levels remained above expected values for untreated individuals after 15 years of hydroxyurea therapy. The Discussion says hematologic effects were sustained and found no apparent tolerance among patients with adequate adherence. Rather than reporting a waning HbF response, this cohort's findings point to a sustained one. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“BCL11A is a repressor of HbF gene expression.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [4] Akinsheye, 2011, Fetal hemoglobin in sickle cell anemia, Blood source
The Introduction describes the suppressive effects of BCL11A on HBG expression. It hedges the mechanism by which BCL11A acts, not its repressive role. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [14] Menzel, 2007, A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15, Nat Genet source
- Partly supportedcites [15] Sedgewick, 2008, BCL11A is a major HbF quantitative trait locus in three different populations with β-hemoglobinopathies, Blood Cells Mol Dis sourceExperimental — accuracy not yet measured
The Results and Discussion section (page unavailable) says BCL11A functions as a transcriptional repressor and that its variants are associated with HbF levels. It also says the mechanism by which BCL11A modulates HbF production was not understood; it does not establish that BCL11A represses HbF gene expression specifically. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Inactivation and activation of genes within the b-globin gene cluster holds the keys to reactivating for therapeutic gain the usually dormant HbF genes.[6][7][8][9][10][11][12]”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [6] Ikawa, 2019, Gene therapy of hemoglobinopathies: progress and future challenges, Hum Mol Genet source
- Supportedcites [7] Vinjamur, 2018, Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies, Br J Haematol source
The ‘Cis-acting sequences that control fetal globin expression’ section says that recruiting transcriptional activators to fetal-globin promoters could reactivate HbF. The ‘Current switching-based therapy efforts’ section describes disrupting sequences in the β-globin locus that silence HBG genes to induce HbF. Page numbers were not supplied in our copy. (LLM, conf=0.91)
- Supportedcites [8] Blobel, 2015, An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference, Exp Hematol source
The section “Transcription factor pathways involved in globin gene switching” describes reactivating fetal γ-globin in adult cells as a potential therapy and reports that a mutation in the γ-globin promoter activates fetal globin genes. It also discusses repression of γ-globin and therapeutic approaches to reversing it. The supplied passages do not give page numbers. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The most efficient means of treatment is interrupting disease pathophysiology by preventing deoxyHbS polymerization.”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Partly supportedcites [5] Eaton, 2017, Treating sickle cell disease by targeting HbS polymerization, Blood sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) identifies HbS polymerization as the root cause of sickle cell pathology and argues for directing more research and trials toward inhibiting it. It does not establish that preventing polymerization is the most efficient treatment; the Conclusion (page unavailable) says polymerization inhibitors still face hurdles before clinical use. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“HbF is variably increased in nearly all HbS homozygotes.4”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Partly supportedcites [4] Akinsheye, 2011, Fetal hemoglobin in sickle cell anemia, Blood sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) defines sickle cell anemia as HbS homozygosity and says HbF levels remain above normal in most patients. It also describes substantial variation in HbF levels. The source says “most,” not “nearly all,” so the claim overstates how many patients have increased HbF. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The rate and extent of polymerization is modified by the erythrocyte HbF concentration. 2”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [2] Eaton, 1987, Hemoglobin S gelation and sickle cell disease, Blood source
In “Hemoglobin S Gelation and Sickle Cell Disease” (p. 1258, Fig. 9), the paper relates the fraction of HbF in an HbS mixture to the gelation delay time, a measure of polymerization rate. The same section says HbF has a marked effect on gelation, while its discussion of HbS–HbF solubility addresses the amount polymerized at equilibrium. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This can be accomplished by inducing sufficiently high levels of HbF in most sickle erythrocytes.5”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [5] Eaton, 2017, Treating sickle cell disease by targeting HbS polymerization, Blood source
The “Induce HbF synthesis” section says that HbF inhibits HbS polymerization and that treatment would be more effective if increased HbF were distributed among more red cells. It identifies inducing HbF synthesis in as many red cells as possible as a focus of current research. The paper describes inhibition rather than requiring complete elimination of polymerization. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The sentinel SNP marking this QTL is rs1427407.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [19] Bauer, 2013, An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level, Science source
In the passage labeled Abstract (page not provided), the paper identifies rs1427407 as the SNP with the strongest association with fetal hemoglobin level among the common variants tested in the BCL11A enhancer. This supports describing it as the sentinel SNP for that QTL. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Disruption of BCL11A and ZBTB7A binding sites led to 30% to 40% g globin and 75% to 80% F-cells.27”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [27] Weber, 2020, Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype, Sci Adv sourceExperimental — accuracy not yet measured
The Results section (page not available) reports that editing the LRF/ZBTB7A or BCL11A binding sites separately increased γ-globin expression and produced approximately 74–81% F-cells in RBCs derived from sickle-cell HSPCs. It does not establish the stated 30–40% γ-globin range: for the −197 LRF-site edit, it reports 48 ± 3% of β-like globin transcripts. The Discussion describes simultaneous disruption of both sites as a future strategy, not the experiment yielding these results. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- Probably not a substantial claim. 12
- It may state two separate claims as one. 48
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“When HbF/F-cell is 9 to 12 pg, calculations suggested that deoxyHbS polymerization should be prevented at physiologic venous and capillary O 2 saturations of 40% to 70%, affording the sickle erythrocyte nearly total protection from HbS polymerinduced damage, although recent studies call into question this observation.3,48,49”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Disputedcites [3] Henry, 2020, Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease, Proc Natl Acad Sci USA sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Disputedcites [48] Maier-Redelsperger, 1994, Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease, Blood sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [49] Horiuchi, 1995, Estimation of fetal hemoglobin levels in individual red cells via fluorescence image cytometry, Cytometry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“As HbF falls and fewer F-cells are protected from HbS polymer damage, the propensity for vascular occlusion and intravascular hemolysis increases with the release of heme products into the circulation that scavenge nitric oxide causing endothelial damage and vasculopathy.[57][58][59]”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Disputedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Several approaches to reducing the expression of HbF suppressors in CD34 1 cells have entered clinical trials, including the first use of CRISPR-Cas9 in humans (Figure 2).123-125”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not checked — no full text of the sourcecites [123] Porteus, 2017, Genome Editing for the β-Hemoglobinopathies, Adv Exp Med Biol source
- Disputedcites [124] Hoban, 2016, Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease, Blood sourceExperimental — accuracy not yet measured
The 'Current SCD gene therapy clinical trials' section describes trials using globin gene-addition vectors, including one treatment with an antisickling β-globin vector. The paper discusses BCL11A suppression and CRISPR-based editing as novel approaches, not as approaches that had entered clinical trials; it does not report a first use of CRISPR-Cas9 in humans. Page numbers were not available in our copy. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“HbF prolongs the time needed for HbS polymerization (delay time), allowing the escape of sickle erythrocytes from the microcirculation into larger veins and hence the lungs, where on reoxygenation, HbS polymer melts.3”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Supportedcites [3] Henry, 2020, Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease, Proc Natl Acad Sci USA source
The Discussion (Fig. 12; page unavailable) describes a delay that lets red cells pass through narrow vessels, followed by fiber melting when they return to the lungs and are reoxygenated. It also says delay times are much longer in S/HPFH, the HbF-containing condition compared in the Results (Fig. 11; page unavailable). (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“BCL11A expression is controlled by transcriptional and/or translational mechanisms.[22][23][24]”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [22] Basak, 2020, Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation, Nat Genet source
The Abstract states that BCL11A is regulated at the level of mRNA translation during human hematopoietic development and identifies LIN28B-mediated suppression of that translation. This supports the claim’s “and/or” formulation through its translational component. (LLM, conf=0.92)
- Supportedcites [23] Lessard, 2018, 14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts, Hum Mol Genet source
The Introduction (page not provided) says variants disrupt a developmental-stage-specific enhancer of BCL11A, supporting transcriptional control of its expression. It also reports that miR-486-3p directly targets BCL11A in erythroid cells, consistent with the claim’s broader description of regulatory mechanisms. (LLM, conf=0.87)
- Could not verifycites [24] Huang, 2017, Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element, Genes Dev sourceExperimental — accuracy not yet measured
The Abstract describes BCL11A as a repressor of γ-globin transcription, and the Results examine what happens when BCL11A is knocked out. Neither passage addresses whether BCL11A’s own expression is controlled transcriptionally or translationally; searches for those mechanisms found no supporting passage in our copy. (LLM, conf=0.77)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ZBTB7A is not polymorphic and does not account for HbF variation in patients with sickle cell anemia.26”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [26] Shaikho, 2016, Variants of ZBTB7A (LRF) and its β-globin gene cluster binding motifs in sickle cell anemia, Blood Cells Mol Dis sourceExperimental — accuracy not yet measured
In the paper’s discussion of ZBTB7A variants (page unavailable), the authors conclude that common variants in ZBTB7A or its nearby regulatory regions are unlikely to account for HbF variation in sickle cell anemia. But they report a CGC insertion polymorphism in two patients, so the claim that ZBTB7A is not polymorphic is incorrect. The claim also states the HbF conclusion more definitively than the paper does. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Its inactivation in HUDEP-2 cells led to ;50% HbF; BCL11A plus ZBTB7A knockout caused .90% HbF. 25”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Partly supportedcites [25] Masuda, 2016, Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin, Science sourceExperimental — accuracy not yet measured
The HUDEP-2 results report HbF above 60% in all three ZBTB7A-knockout clones, not approximately 50%. The double-knockout results report HbF at 91–94% of total hemoglobin, supporting the second figure. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“BCL11A binds TGACCA motifs in the HBB gene cluster, preferentially binding to position 2115 in the HBG2 and HBG1 promoters.20,21”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Supportedcites [20] Liu, 2018, Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch, Cell source
The Results section, “High-resolution localization of BCL11A at the γ-globin promoters” (page not supplied), reports preferential binding to the distal TGACCA motif at −118 to −113, which includes position −115. The Methods section identifies the duplicated promoters as HBG1 and HBG2. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [21] Martyn, 2018, Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding, Nat Genet source
plaindirect- Asserted: unclear — It is unclear whether the authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Kr üppel-like factor 1 (KLF1) binds to the promoter of ZBTB7A increasing its expression; KLF1 also activates the expression of BCL11A.28,29”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [28] Norton, 2017, KLF1 directly activates expression of the novel fetal globin repressor ZBTB7A/LRF in erythroid cells, Blood Adv source
- Partly supportedcites [29] Bieker, 2010, Putting a finger on the switch, Nat Genet sourceExperimental — accuracy not yet measured
The Common ties section reports that KLF1 binds the BCL11A gene and that BCL11A levels rise with KLF1 levels, supporting the BCL11A part of the claim. Our copy does not mention ZBTB7A or say that KLF1 binds its promoter or increases its expression. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The HbS gene had a single origin in West Central Africa or in the Sahara during the Holocene Wet Phase between 3400 and 11 100 years ago or in agriculturists ;22 000 years ago, which was introduced into rainforest dwellers within the last 6000 years.32,33”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Partly supportedcites [32] Shriner, 2018, Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase, Am J Hum Genet sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [33] Laval, 2019, Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure, Am J Hum Genet source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This variant explained ;10% of HbF variability compared with ;8% for BCL11A.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Supportedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol source
The Results section reports that, in Arab-Indian haplotype sickle cell patients, the regression model for ANTXR1 rs4527238 explained about 10% of HbF variability, compared with about 8% for BCL11A rs1427407. These are the figures attributed to the source; the finding is specific to that patient group. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [42] Al-Ali, 2018, ANTXR1 intronic variants are associated with fetal hemoglobin in the Arab-Indian haplotype of sickle cell disease, Acta Haematol source
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The AI haplotype in Saudi patients is associated with a unique pattern of SNPs in putative cis-acting globin regulatory elements and is linked to a novel variant in ANTXR1.40,41”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Partly supportedcites [40] Vathipadiekal, 2016, Homozygosity for a haplotype in the HBG2-OR51B4 region is exclusive to Arab-Indian haplotype sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Results (“A unique AI haplotype”) and Discussion describe a distinctive SNP haplotype in Saudi AI patients that may involve cis-acting globin regulatory elements. The paper does not report a link to a novel ANTXR1 variant; a search for ANTXR1 found no matching passage in our copy. Page numbers were not provided. (LLM, conf=0.88)
- Partly supportedcites [41] Vathipadiekal, 2016, A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes a unique cis-acting sub-haplotype containing putative functional elements in the AI haplotype, but does not establish the claimed pattern of SNPs in Saudi patients. The Results (page unavailable) identify ANTXR1 SNPs associated with fetal hemoglobin specifically in Saudi AI-haplotype patients; they do not show that the AI haplotype itself is linked to a novel ANTXR1 variant. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The earlier origin in agriculturists might have resulted from destruction of the rain forest canopy that created conditions favorable for malaria.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Could not verifycites [32] Shriner, 2018, Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase, Am J Hum Genet sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) estimates that the sickle allele arose about 7,300 years ago and mentions the equatorial rainforest as a possible place of origin. It does not address an earlier origin in agriculturists or propose that destruction of the rainforest canopy created conditions favorable for malaria. Searches for agriculturists and forest clearing found no supporting passage. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [33] Laval, 2019, Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure, Am J Hum Genet source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As HbF levels decline, AI haplotype adults have more numerous symptoms, and their disease begins to resemble that of African patients, but with a lower incidence of stroke, no leg ulcers, and .70%prevalence of splenomegaly.37,38”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [37] Perrine, 1972, Benign sickle-cell anaemia, Lancet source
- Partly supportedcites [38] Alsultan, 2014, Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign, Br J Haematol sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says the adult Arab–Indian haplotype phenotype is broadly similar to that of African-haplotype patients, except for fewer overt strokes, no leg ulcers, and more persistent splenomegaly. It proposes declining HbF as an explanation for the change from the milder childhood phenotype, but the Results report only that a majority had a palpable spleen; the copy does not establish prevalence above 70%. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Individuals with this genotype do not have hemolytic anemia and are usually asymptomatic.50”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Supportedcites [50] Ngo, 2012, Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin, Br J Haematol source
The Discussion states that HbS-HPFH has “little or no haemolysis” and nearly normal haematological values. The Results report an absence of symptoms due to sickle cell anaemia. Page numbers were not provided for these passages. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When HbF is near 30%, disease can be relatively benign and 70% of cells can be protected.[52][53][54]”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
- Not checked — no full text of the sourcecites [53] Perrine, 1978, Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects, Ann Intern Med source
- Partly supportedcites [54] Perrine, 1981, Sickle cell disease in Saudi Arabs in early childhood, Arch Dis Child sourceExperimental — accuracy not yet measured
The Results report a mean HbF level of 29% in one group of Saudi Arab infants with HbSS, and the introductory passage says the unusually high HbF is believed to account for their relatively mild clinical course. The paper does not report that 70% of cells were protected; the Subjects and methods passage describes HbF distribution as heterocellular without giving a protected-cell percentage. Page numbers were not available in our copy. (LLM, conf=0.87)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“High HbF is strongly associated with a reduced rate of acute painful episodes, fewer leg ulcers, and longevity.55”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Supportedcites [55] Steinberg, 2012, Genetic modifiers of sickle cell disease, Am J Hematol source
The HbF section states the cited claim verbatim: high HbF is strongly associated with fewer acute painful episodes, fewer leg ulcers, and longevity. The paper notes some studies with differing results but presents this as its overall assessment. (LLM, conf=0.95)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of 375 children with sickle cell anemia or Figure 1.HbF distribution in sickle erythrocytes from 3 patients with 20% HbF.An example of 3 possible distributions of HbF/F-cell in 1000 cells from 3 individuals with mean HbF levels of 20%.The y axis represents numbers of cells, and the x axis represents HbF concentration in 5-pg increments.In red are cells likely to be least protected from HbS polymer”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Partly supportedcites [69] Sommet, 2016, Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study, Br J Haematol sourceExperimental — accuracy not yet measured
The cohort table lists 375 children, and the Cerebral vasculopathy and stroke section reports 59 with cerebral vasculopathy, including seven who had a stroke. The paper gives 4.4 years as the median age at cerebral vasculopathy diagnosis, not the mean. Its risk-factor table reports HbF as protective against cerebral vasculopathy (HR 0.68, 95% CI 0.48–0.96, per 5% increase). (LLM, conf=0.90)
plaindirectn = 375 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Acute painful episodes and acute chest syndrome are a result of sickle vasoocclusion; HbF has the most noticeable beneficial effect on these subphenotypes.”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Supportedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest source
The “Evidence that hemolysis modulates SCD subphenotypes” section identifies subphenotypes associated with sickle vaso-occlusion and says HbF has its most robust effects on them, including acute chest syndrome. Table 1 in “The hemolysis hypothesis” lists HbF as protective against both painful episodes and acute chest syndrome. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Priapism, nephropathy, and sickle vasculopathy are associated with hemolysis.”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [57] Kato, 2007, Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes, Blood Rev source
- Supportedcites [58] Kato, 2017, Intravascular hemolysis and the pathophysiology of sickle cell disease, J Clin Invest source
The Abstract links products of hemolysis to vasculopathy and lists priapism and chronic kidney disease among its complications. The section “Hemolytic anemia and vasculopathic complications” also describes hemolytic anemia as a risk factor for vasculopathic complications and associates indices of hemolytic anemia with priapism. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“To identify prognostic factors for clinical complications, 57 infants were studied at 4.4 6 1 months of age and followed for ;19 months.HbF, which fell from 42% to 21% during the observation period, was the strongest prognostic factor for disease complications.64”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Supportedcites [64] Brousse, 2018, Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study, Am J Hematol source
The Abstract reports 57 infants enrolled at a mean age of 4.4 ± 1 months and a median follow-up of 19.4 months. Table 1 gives HbF as 42% at enrollment; the Biological data discussion reports 21% at 24 months and calls early HbF the most robust predictor of severe outcomes in the first two years. Page numbers are unavailable in our copy. (LLM, conf=0.94)
plaincorrelationaln = 57- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of 230 children treated with hydroxyurea with 510 patient-years of follow-up, patients with HbF less than 20% had twice the risk of hospitalization for pain and acute chest syndrome and 2 times the risk of fever as patients with .20%HbF.65”
§ Fetal hemoglobin in sickle cell anemia > HbF and survival
What the sources say
- Partly supportedcites [65] Estepp, 2017, A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy, Am J Hematol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelationaln = 230- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CRISPR-Cas dominates the field because of the ease of using guide RNAs directing the CRISPR complex to specific DNA sequences and the increasing ability to target most sites in the genome.121,122”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Partly supportedcites [121] Doudna, 2020, The promise and challenge of therapeutic genome editing, Nature sourceExperimental — accuracy not yet measured
The GENOME EDITING STRATEGIES section (page unavailable) says CRISPR-Cas9 was widely adopted because its DNA-binding and editing capabilities are easy to program, and explains how guide RNA directs it to a complementary DNA sequence. It also describes an expanding collection of enzymes, but does not establish that most genomic sites can be targeted; the section notes a PAM requirement for Cas9 binding. (LLM, conf=0.83)
- Partly supportedcites [122] Walton, 2020, Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants, Science sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says that SpRY makes the vast majority of the genome targetable, supporting the claim about increasing targeting range. The passages do not say that CRISPR-Cas dominates genome editing because guide RNAs make it easy to direct the complex to specific sequences. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Preclinical testing in sickle CD34 1 cells transduced with this shRNA miR achieved a vector copy .5 and gene marking of .80%, resulting in a three-to fivefold induction of HbF.Growth, differentiation, and engraftment of gene-modified cells in vitro or in vivo were unaffected.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Partly supportedcites [119] Brendel, 2020, Preclinical evaluation of a novel lentiviral vector driving lineage-specific BCL11A knockdown for sickle cell gene therapy, Mol Ther Methods Clin Dev sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hydroxyurea started at ;11 months at a dose of ;27 mg/kg was associated with HbF levels of 33.3 6 9.1%; 33% of patients had HbF .40% with a hemoglobin concentration of 10.1 6 1.3 g/dL; acute events were markedly reduced; and toxicity was minimal.89”
§ Fetal hemoglobin in sickle cell anemia > Hydroxyurea
What the sources say
- Partly supportedcites [89] McGann, 2019, Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia, Am J Hematol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“They include disrupting the erythroid enhancer of BCL11A or the binding sites for BCL11A in the g-globin gene promoters.126”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [126] Métais, 2019, Genome editing of HBG1 and HBG2 to induce fetal hemoglobin, Blood Adv source
The Introduction identifies disruption of BCL11A-binding sites in the HBG1 and HBG2 (γ-globin) promoters as the strategy studied. The Discussion also describes editing an erythroid-specific enhancer in BCL11A as a comparable approach. No page numbers are available in our copy. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This same approach was used in a patient with sickle cell anemia.About 1 copy of this vector was present in each cell.After 15 months, total hemoglobin level was 11 to 12 g/dL; HbA T87Q formed about half of the total hemoglobin; and the patient was asymptomatic.117”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Supportedcites [117] Ribeil, 2017, Gene therapy in a patient with sickle cell disease, N Engl J Med source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Gene therapy will also have to compete with the improving prospects for haploidentical allogeneic transplantation that could extend the proven effectiveness of allogeneic transplantation.128”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Supportedcites [128] Leonard, 2020, Curative options for sickle cell disease: haploidentical stem cell transplantation or gene therapy?, Br J Haematol source
The “Haploidentical transplantation versus gene therapy” section compares the two curative strategies as haploidentical HSCT methods are refined. The “Haploidentical transplantation results in sickle cell disease” section says improved engraftment could expand this curative option to nearly all patients with SCD. Together, these passages support the claim that improving haploidentical transplantation presents an alternative with which gene therapy must compete. (LLM, conf=0.92)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
In the paper
“It is nearly impossible to have a clinically important number of fully protected F-cells when HbF is 5%; no more than 15% of cells can be protected when HbF is 10%.52”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [52] Steinberg, 2014, Fetal hemoglobin in sickle cell anemia: a glass half full?, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Reduction of let-7 or overexpression of its regulator LIN28B is associated with increased HBG expression. 13”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [13] Lee, 2013, LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sickle cell disease is caused by homozygosity for the sickle hemoglobin (HbS) gene (b 7glu-val , GAG-GTG) or compound heterozygosity of the HbS gene and other HBB disorders.1”
§ Fetal hemoglobin in sickle cell anemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [1] Piel, 2017, Sickle cell disease, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease.”
§ Fetal hemoglobin in sickle cell anemia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Only HBG2 expression is affected by the 2158 polymorphism; both HbF genes are affected by BCL11A polymorphisms.30”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
What the sources say
- Not checked — no full text of the sourcecites [30] Shaikho, 2018, Cis- and trans-acting expression quantitative trait loci differentially regulate gamma-globin gene expression, bioRxiv source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“From the primordial haplotype the HbS gene subsequently became associated with 5 common HBB haplotypes: Bantu (CAR or Central African Republic), Cameroon, Arab-Indian (AI), Senegal, and Benin.34”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not matchedcites [34] Nagel RL , SteinbergMH. Genetics of the βs gene: origins, genetic epidemiology, and epistasis in sickle cell anemia. In: SteinbergM, ForgetBG, HiggsDR, NagelRL, eds.Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management, Cambridge, United Kingdom: Cambridge University Press; 2001:711-755.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Benin haplotype patients of African descent have HbF of ;6%; Saudi Arab patients with the Benin haplotype have HbF of ;11%.36”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [36] Alsultan, 2011, Fetal hemoglobin in sickle cell anemia: Saudi patients from the Southwestern province have similar HBB haplotypes but higher HbF levels than African Americans, Am J Hematol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“making it unsurprising that targeting the HBG2 site had a smaller effect on HbF.”
§ Fetal hemoglobin in sickle cell anemia > Quantitative trait loci associated with HbF
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Each haplotype is associated with a distinctive mean HbF level, albeit with wide dispersion, making ascertainment of haplotype in individuals of little prognostic value.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Adult HbS homozygotes with the AI haplotype have a mean baseline HbF of 17% 35 ; Senegal haplotype patients have HbF of ;10%.”
§ Fetal hemoglobin in sickle cell anemia > HbF, geography, and HBB haplotypes
What the sources say
- Not checked — no full text of the sourcecites [35] Al-Ali, 2020, Prevalence and diversity of haplotypes of sickle cell disease in the Eastern Province of Saudi Arabia, Hemoglobin source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This protection provided by HbF can be nearly absolute or only partial.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HbF is distributed nearly evenly, or pancellularly, in HbS-HPFH erythrocytes, endowing each cell with ;10 pg HbF; HbS polymer is not present in these erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Treatment with hydroxyurea increases the number of F-cells and the concentration of HbF/F-cell.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In sickle cell anemia, HbS polymer is present at 70% O 2 saturation, and the polymer fraction rises steeply as O 2 saturation falls.51”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
What the sources say
- Not checked — no full text of the sourcecites [51] Brittenham, 1985, Hemoglobin S polymerization: primary determinant of the hemolytic and clinical severity of the sickling syndromes, Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with untreated sickle cell anemia, sickle cell anemia treated with hydroxyurea or HbS-db thalassemia, who can have total HbF levels similar to those found in HbS-HPFH, are usually symptomatic; all have hemolytic anemia.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Each erythrocyte contains ;30 pg hemoglobin.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with sickle cell anemia have 2% to 80% F-cells, which survive longer than non-HbF cells.”
§ Fetal hemoglobin in sickle cell anemia > F-cells: heterogeneity of HbF concentrations
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In these complications HbF has a less obvious beneficial effect, perhaps because only a small number of lysed sickle erythrocytes are needed to trigger these subphenotypes.59”
§ Fetal hemoglobin in sickle cell anemia > HbF effects on clinical and hematologic phenotypes
What the sources say
- Not checked — no full text of the sourcecites [59] Reiter, 2002, Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease, Nat Med source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Pre-hydroxyurea era studies of patients with a mean age of 14.1 6 12.7 years suggested that neither stroke nor silent cerebrovascular disease was associated with HbF.66,67”
§ Fetal hemoglobin in sickle cell anemia > HbF and cerebrovascular disease
What the sources say
- Not matchedcites [66] Ohene-Frempong, 1998, Cerebrovascular accidents in sickle cell disease: rates and risk factors, Blood
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [67] Kinney, 1999, Silent cerebral infarcts in sickle cell anemia: a risk factor analysis, Pediatrics source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Correcting the HbS mutation itself requires a slightly different approach relying on homology-directed repair, which as currently used, is a less efficient reparative pathway.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cell-mediated therapy either adds a b-globin gene with a HbF-like substitution or reverses the silencing of the HbF genes by curbing HbF repressors or disrupting their binding motifs in g-globin gene promoters.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This has not yet been achieved with drug therapy but might be possible with cell-based therapeutics.”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Using a modified manufacturing process, 13 patients had plerixafor mobilized CD34 1 cells transfected with the HbA T87Q -containing vector and were followed for 3 to 15 months.The vector copy number was 3.8, HbA T87Q was nearly 50% of total hemoglobin, and hemoglobin levels were 10.2 to 15 g/dL; patients became asymptomatic.118”
§ Fetal hemoglobin in sickle cell anemia > Cell-based HbF-inducing therapeutics
What the sources say
- Not checked — no full text of the sourcecites [118] Kanter, 2019, Resolution of sickle cell disease manifestations in patients treated with lentiglobin gene therapy: updates results from the phase 1/2 HGB-206 group C study, Blood source
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Other drugs that act epigenetically or with novel mechanisms of action have increased HbF levels in preclinical and early-phase clinical trials; none are approved for treatment.”
§ Fetal hemoglobin in sickle cell anemia > Novel agents and targets
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The baseline HbF of 9.1% increased to 25.9% after 2 months and appeared to stabilize between 46% and 48% when tested at 4 through 9 months”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many of these studies had follow-up of more than 1 year, with near normalization of the hematologic findings.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cell-based therapeutics are developing rapidly.”
§ Fetal hemoglobin in sickle cell anemia > Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genomic editing and shRNA-mediated knockdown of BCL11A should erase lingering doubts that the clinical and hematologic phenotypes of sickle cell anemia can be reversed by high HbF levels in most sickle erythrocytes.”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: BCL11A is one of two major repressors of HbF gene expression.
- Rests on an assumption: BCL11A expression is controlled by an erythroid-specific enhancer.
- Rests on an assumption: BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.
- Rests on an assumption: CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer or its binding sites in the HbF gene promoters reverses the repression of these genes increasing HbF.
In the paper
“Two patients with b thalassemia treated similarly achieved HbF .97% of the hemolysate with a hemoglobin concentration at 15 months of 14 g/dL.125”
§ Fetal hemoglobin in sickle cell anemia > MBD2-NuRD
What the sources say
- Not matchedcites [125] Corbacioglu, 2020, Initial safety and efficacy results with a single dose of autologous crispr-cas9 modified CD34+ hematopoietic stem and progenitor cells in transfusion-dependent β-thalassemia and sickle cell disease, Eur Soc Haematol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper relies on this without support.
Gene therapy does not require immunosuppression.
“Gene therapy does not require the immunosuppression.”
The paper relies on this without support.
Experience with allogeneic transplantation is far greater than with gene therapy.
“Nevertheless, experience with allogeneic transplantation is far greater”
The paper relies on this without support.
Myeloablative conditioning is required for all cell-based therapeutics.
“Myeloablative conditioning is required for all cell-based therapeutics”
The paper relies on this without support.
Genomic editing does not use lentiviral transduction.
“Genomic editing does not use lentiviral transduction.”
The paper relies on this without support.
BCL11A is one of two major repressors of HbF gene expression.
“The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer.”
The paper relies on this without support.
BCL11A expression is controlled by an erythroid-specific enhancer.
“The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer.”
The paper relies on this without support.
BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.
“BCL11A binds to a TGACCA motif centered at position 2115 in the promoters of both HBG2 and HBG1.”
The paper relies on this without support.
CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer or its binding sites in the HbF gene promoters reverses the repression of these genes increasing HbF.
“CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer, shown as a double-strand break, or its binding sites in the HbF gene promoters, shown before editing, reverses the repression of these genes increasing HbF.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Patients with TDT or SCD who co-inherit hereditary persistence of fetal hemoglobin, in which fetal expression continues into adulthood, have little or no disease.25”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [25]
Experimental — accuracy not yet measured
Citations
Cites
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320
Self-citationEffect of hydroxyurea on the frequency of painful crises in sickle cell anemia
Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322001 · Cited by 2,340
Cerebrovascular accidents in sickle cell disease: rates and risk factors.
(1998) · PubMed · doi:10.1182/blood.v91.1.288 · Cited by 1,694
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510865 · Cited by 1,488
Self-citationCell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease
Reiter, C. D., Wang, X., Tanus-Santos, J. E., Hogg, N., Cannon, R. O., Schechter, A. N., & Gladwin, M. T. (2002) · Nature Medicine · doi:10.1038/nm1202-799 · Cited by 1,330
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P. (2020) · Science · doi:10.1126/science.aba8853 · Cited by 1,233
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126
Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease
Reiter, C. D., Wang, X., Tanus-Santos, J. E., et al. (2002) · Nature Medicine · doi:10.1038/nm799 · Cited by 1,097
Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A
Sankaran, V. G., Menne, T. F., Xu, J., Akie, T. E., Lettre, G., Van Handel, B., Mikkola, H. K. A., Hirschhorn, J. N., Cantor, A. B., & Orkin, S. H. (2008) · Science · doi:10.1126/science.1165409 · Cited by 919
Kato, G. J., Gladwin, M. T., & Steinberg, M. H. (2007) · Blood Reviews · doi:10.1016/j.blre.2006.07.001 · Cited by 876
Self-citation
Research works printed but not linked: 1
- Nagel RL , SteinbergMH. Genetics of the βs gene: origins, genetic epidemiology, and epistasis in sickle cell anemia. In: SteinbergM, ForgetBG, HiggsDR, NagelRL, eds.Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management, Cambridge, United Kingdom: Cambridge University Press; 2001:711-755.
Cited by
Sorted by citations
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2031054 · Cited by 1,962
Self-citationExagamglogene Autotemcel for Severe Sickle Cell Disease
Frangoul, H., Locatelli, F., Sharma, A., Bhatia, M., Mapara, M., Molinari, L., Wall, D., Liem, R. I., Telfer, P., Shah, A. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309676 · Cited by 493
Self-citationBiologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease
Kanter, J., Walters, M. C., Krishnamurti, L., Mapara, M. Y., Kwiatkowski, J. L., Rifkin-Zenenberg, S., Aygun, B., Kasow, K. A., Pierciey, F. J., Bonner, M., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2117175 · Cited by 442
Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia
Locatelli, F., Lang, P., Wall, D., Meisel, R., Corbacioglu, S., Li, A. M., de la Fuente, J., Shah, A. J., Carpenter, B., Kwiatkowski, J. L., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309673 · Cited by 253
Identification of non-coding silencer elements and their regulation of gene expression
Pang, B., van Weerd, J. H., Hamoen, F. L., & Snyder, M. P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00549-9 · Cited by 103
Potent and uniform fetal hemoglobin induction via base editing
Mayuranathan, T., Newby, G. A., Feng, R., Yao, Y., Mayberry, K. D., Lazzarotto, C. R., Li, Y., Levine, R. M., Nimmagadda, N., Dempsey, E., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01434-7 · Cited by 86
ZNF410 represses fetal globin by singular control of CHD4
Vinjamur, D. S., Yao, Q., Cole, M. A., McGuckin, C., Ren, C., Zeng, J., Hossain, M. A., Luk, K., Wolfe, S. A., Pinello, L., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00843-w · Cited by 83
Activation of γ-globin expression by hypoxia-inducible factor 1α
Feng, R., Mayuranathan, T., Huang, P., Doerfler, P. A., Li, Y., Yao, Y., Zhang, J., Palmer, L. E., Mayberry, K. D., Christakopoulos, G. E., et al. (2022) · Nature · doi:10.1038/s41586-022-05312-w · Cited by 69
Exagamglogene Autotemcel: First Approval
Hoy, S. M. (2024) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-024-00696-z · Cited by 64
“…of γ-globin with β-globin: it silences the expression of γ-globin and consequently lowers foetal haemoglobin levels in adult human erythroid cells [2, 3]. β-haemoglobinopathies [e.g. transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD)] result from mutations in the haemoglobin…”
Bou‐Fakhredin, R., Franceschi, L. D., Motta, I., Cappellini, M. D., & Taher, A. T. (2022) · Pharmaceuticals · doi:10.3390/ph15060753 · Cited by 56
“The three main loci that control HbF levels outside of the locus control region at the 5' end of the β-globin gene cluster and promoter regions on the β- and γ-globin genes are BCL11A, ZBTB7A and MYB [15].”
BackgroundInfluentialIn vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies
Li, C. L., Georgakopoulou, A., Newby, G. A., Everette, K. A., Nizamis, E., Paschoudi, K., Vlachaki, E., Gil, S., Anderson, A. K., Koob, T., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.162939 · Cited by 47
Autologous gene therapy for hemoglobinopathies: From bench to patient’s bedside
Locatelli, F., Cavazzana, M., Frangoul, H., de la Fuente, J., Algeri, M., & Meisel, R. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.005 · Cited by 43
Base Editing of HBG1 and HBG2 Promoters for Sickle Cell Disease
Gupta, A. O., Sharma, A., Frangoul, H., Kanter, J., Mapara, M. Y., Dalal, J. D., Alavi, A., Jaroscak, J., Ayala, E., DiPersio, J. F., et al. (2026) · New England Journal of Medicine · doi:10.1056/nejmoa2504835 · Cited by 45
Elevating fetal hemoglobin: recently discovered regulators and mechanisms
Khandros, E., & Blobel, G. A. (2024) · Blood · doi:10.1182/blood.2023022190 · Cited by 32
Genetic therapies for the first molecular disease
Doerfler, P. A., Sharma, A., Porter, J. S., Zheng, Y., Tisdale, J. F., & Weiss, M. J. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146394 · Cited by 30
“It is estimated that 9–12 pg HbF per RBC can block HbS polymerization in venous capillary beds (179).”
BackgroundInfluentialCRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell Disease
Hanna, R., Frangoul, H., Piñeiro, L., McKinney, C. M., Mapara, M. Y., Dalal, J. D., Rangarajan, H. G., Atkins, H., Sharma, A., Chang, K., et al. (2026) · New England Journal of Medicine · doi:10.1056/nejmoa2415550 · Cited by 28
A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease
Rampersaud, E., Kang, G., Palmer, L. E., Rashkin, S. R., Wang, S., Bi, W., Alberts, N. M., Anghelescu, D. L., Barton, M., Birch, K., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2021004634 · Cited by 28
Acute chest syndrome of sickle cell disease: genetics, risk factors, prognosis, and management
Klings, E. S., & Steinberg, M. H. (2022) · Expert Review of Hematology · doi:10.1080/17474086.2022.2041410 · Cited by 29
“and are loosely associated with overall severity of disease through their characteristic HbF levels [52].”
BackgroundMethodInfluentialSelf-citationNovel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders
Pinto, V. M., Mazzi, F., & Franceschi, L. D. (2024) · Blood · doi:10.1182/blood.2023022193 · Cited by 28
Lebenthal, J. M., Kontoyiannis, P. D., Hahn, A. W., et al. (2024) · European Urology Oncology · doi:10.1016/j.euo.2024.07.002 · Cited by 24
Han, Y., Tan, X., Jin, T., Zhao, S., Li, H., Zhang, W., Kurita, R., Nakamura, Y., Liu, J., Li, D., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174788 · Cited by 21
Neutrophils as drivers of vascular injury in sickle cell disease
Torres, L. S., & Hidalgo, A. (2022) · Immunological Reviews · doi:10.1111/imr.13146 · Cited by 22
Sickle cell disease in the Eastern Province of Saudi Arabia: Clinical and laboratory features
Al‐Ali, A. K., Alsulaiman, A., Alfarhan, M. F. A., Safaya, S., Vatte, C., Albuali, W. H., Qutub, H. O., Alzahrani, A. J., Milton, J. N., & Steinberg, M. H. (2021) · American Journal of Hematology · doi:10.1002/ajh.26096 · Cited by 19
Self-citationBelcher, J. D., Nataraja, S. G., Abdulla, F. A., Zhang, P., Chen, C., Nguyen, J., Ruan, C., Singh, M., Demes, S., Olson, L., et al. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1101501 · Cited by 19
“SCD patients with hereditary persistence of F-cells have a more benign clinical course (34).”
Katta, V., O’Keefe, K., Li, Y., Mayuranathan, T., Lazzarotto, C. R., Wood, R. K., Levine, R. M., Powers, A., Mayberry, K. D., Manquen, G., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.07.022 · Cited by 20
Corbacioglu, S., Frangoul, H., Locatelli, F., Hobbs, W., & Walters, M. C. (2023) · American Journal of Hematology · doi:10.1002/ajh.27166 · Cited by 19
“Chronic iron overload in patients with TDT, which persists even after any form of curative approach, perpetuates inflammation and TABLE 1 Important clinical endpoints for curative genetic therapies for TDT. continues to damage sensitive organs such as the liver.”
BackgroundInfluentialDiamantidis, M. D., Ikonomou, G., Argyrakouli, I., Pantelidou, D., & Delicou, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211886 · Cited by 21
Targeting fetal hemoglobin expression to treat β hemoglobinopathies
Steinberg, M. H. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2066519 · Cited by 16
Self-citationRecent advancements in gene therapy for sickle cell disease and β-thalassemia
Li, L., & Mandal, P. K. (2024) · Frontiers in Hematology · doi:10.3389/frhem.2024.1468952 · Cited by 23
“Additional studies are required to assess the safety and ef fi cacy of Lenti-vector GLOBE1. g -Globin is better than b -globin in preventing HbS polymerization and sickling of RBCs (58).”
BackgroundInfluentialRecent advances in “sickle and niche” research - Tribute to Dr. Paul S Frenette -
Torres, L. S., Asada, N., Weiss, M. J., Trumpp, A., Suda, T., Scadden, D. T., & Ito, K. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.06.004 · Cited by 19
“Fetal hemoglobin (HbF, a2g2) expression is a major modifier of clinical severity of SCD and an important therapeutic target (Steinberg, 2020).”
BackgroundGhazaly, E. A., Sajic, M., Rantell, K. R., McBlane, J. W., Johnston, J. D., Niewiarowska, A., Butler, A. S., & Cole, S. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46080485 · Cited by 19
“In patients with SCD, HbF levels constituting ≥ 20% of total hemoglobin have been shown to be protective against vaso-occlusive crises [24].”
BackgroundRespiratory management of acute chest syndrome in children with sickle cell disease
Ahmed, B., Arigliani, M., & Gupta, A. K. (2024) · European Respiratory Review · doi:10.1183/16000617.0005-2024 · Cited by 15
“…A SSAD et al. [14] showed that, in France, the implementation of prevenar-13 (pneumococcal vaccination) led to a 40% reduction in incidence of ACS among children with SCD. Patients with HbSS and HbS-beta 0 -thalassemia face the highest risk for ACS, with higher fetal Hb levels reducing odds [15].”
BackgroundEffective therapies for sickle cell disease: are we there yet?
Crossley, M., Christakopoulos, G. E., & Weiss, M. J. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.07.003 · Cited by 18
Tolu, S. S., & Doren, L. V. (2022) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2022.103533 · Cited by 13
Kunz, J. B., & Tagliaferri, L. (2024) · Transfusion Medicine and Hemotherapy · doi:10.1159/000540149 · Cited by 14
Pharmacologic induction of PGC ‐1α stimulates fetal haemoglobin gene expression
Sun, Y., Habara, A. H., Le, C. Q., Nguyen, N., Chen, R., Murphy, G. J., Chui, D. H. K., Steinberg, M. H., & Cui, S. (2022) · British Journal of Haematology · doi:10.1111/bjh.18042 · Cited by 14
“Rapid Commun Mass Spectrom 2018;32(6):480– 8.”
Self-citationImmunoregulation role of the erythroid cells
Niu, C., & Zhang, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1466669 · Cited by 14
“At the end of the second trimester, erythropoiesis transfers to the bone marrow, which becomes the primary site of erythropoiesis until birth; fetal hemoglobin is produced to facilitate oxygen transport across the placenta during this stage (14).”
BackgroundIs allogeneic transplantation for sickle cell disease still relevant in the era of gene therapy?
Jones, R. J., Kassim, A. A., Brodsky, R. A., & DeBaun, M. R. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024013693 · Cited by 17
Heterogeneity of fetal hemoglobin production in adult red blood cells
Khandros, E., & Blobel, G. A. (2021) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000640 · Cited by 12
Zakaria, O. M., Buhalim, R. A., Jabr, F. A. A., AlSaeed, M. N., Al-Hajji, I. A., Saleh, Y. A. A., Buhalim, M. A., & Dehailan, A. M. A. (2021) · Cureus · doi:10.7759/cureus.19299 · Cited by 12
“With that being said, HbF is an important modulator of the severity of SCD (the higher the levels of HbF, the less severe the disease) [3,4].”
BackgroundTargeting HIF-1α in sickle cell disease and cancer: unraveling therapeutic opportunities and risks
Ubaid, S., Kashif, M., Laiq, Y., Nayak, A., Kumar, V., & Singh, V. K. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2367640 · Cited by 13
“However, elevating Hb targets above 13 g/dl amplifies risks like cardiovascular and cerebrovascular events, vascular access clotting, disease progression, and overall mortality [106,108,109,135].”
BackgroundThe Cas9 Hammer—and Sickle: A Challenge for Genome Editors
Urnov, F. D. (2021) · The CRISPR Journal · doi:10.1089/crispr.2021.29120.fur · Cited by 11
Ranque, B., Diaw, M., Dembélé, A. K., Lapouméroulie, C., Offredo, L., Tessougué, O., Gueye, S. M., Diallo, D. A., Diop, S., Colin, Y., et al. (2023) · British Journal of Haematology · doi:10.1111/bjh.19006 · Cited by 11
Sharma, A., Locatelli, F., Bhatia, M., Molinari, L., Mapara, M. Y., Liem, R. I., Dedeken, L., Wall, D. A., Eckrich, M. J., Kuo, K. H. M., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016701 · Cited by 12
Defining curative endpoints for sickle cell disease in the era of gene therapy and gene editing
Locatelli, F., Corbacioglu, S., Hobbs, W., Frangoul, H., & Walters, M. C. (2023) · American Journal of Hematology · doi:10.1002/ajh.27164 · Cited by 11
“69,70 In addition, pan-cellular expression of HbF across circulating RBCs as measured by F-cell percentage is also a clinically relevant laboratory measure associated with clinical benefit and the absence of VOCs in SCD-HPFH.”
BackgroundSeth, T., Udupi, S., Jain, S., Bhatwadekar, S. S., Menon, N., Jena, R. K., Kumar, R., Ray, S., Parmar, B., Goel, A. K., et al. (2024) · British Journal of Haematology · doi:10.1111/bjh.19829 · Cited by 10
Treating genetic blood disorders in the era of CRISPR-mediated genome editing
Almotiri, A., Abogosh, A., Abdelfattah, A., Alowaisy, D., & Rodrigues, N. P. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.01.031 · Cited by 11
Gotesman, M., Elgar, G., Santiago, L. H., et al. (2022) · In Vivo · doi:10.21873/invivo.12889 · Cited by 9
Emerging therapies and management approaches in sickle cell disease (SCD): A critical review
Patel, S., Patel, R. M., Mukkala, S. R., & Akabari, A. H. (2023) · Journal of Phytonanotechnology and Pharmaceutical Sciences · doi:10.54085/jpps.2023.3.3.3 · Cited by 9
Oshabaheebwa, S., Delianides, C. A., Patwardhan, A. A., Evans, E. N., Sekyonda, Z., Bode, A., Apio, F. M., Mutuluuza, C. K., Sheehan, V., Suster, M. A., et al. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116352 · Cited by 8
Fetal-like Hemoglobin in Sickle Cell Anemia
Steinberg, M. H. (2022) · New England Journal of Medicine · doi:10.1056/nejme2119760 · Cited by 9
Self-citationCRISPR technology in human diseases
Feng, Q., Li, Q., Zhou, H., Wang, Z., Lin, C., Jiang, Z., Liu, T., & Wang, D. (2024) · MedComm · doi:10.1002/mco2.672 · Cited by 8
Lewis, J., Guilcher, G. M. T., & Greenway, S. C. (2024) · European Journal Of Haematology · doi:10.1111/ejh.14247 · Cited by 8
“…the DNMT inhibitor azacytidine was one of the first compounds shown to increase HbF. 10 Decitabine, another DNMT inhibitor which increases HbF, has also been investigated as a treat-ment for SCD. 10,11 However, studies investigating the impact of HU on DNA methylation-related proteins are limited.”
Steinberg, M. H., Kutlar, A., & Sebastiani, P. (2025) · American Journal of Hematology · doi:10.1002/ajh.27729 · Cited by 6
Self-citationHarnessing nucleic acid technologies for human health on earth and in space
Sarli, S. L., & Watts, J. K. (2022) · Life Sciences in Space Research · doi:10.1016/j.lssr.2022.08.006 · Cited by 6
“CRISPR-based therapeutics are being developed for β -thalassemia and sickle cell disease (SCD), two severe monogenic, hematological disorders (Steinberg 2020, Frangoul et al. 2021).”
Verheul, T. C. J., Gillemans, N., Putzker, K., Majied, R., Li, T., Vasiliou, M., Eussen, B., de Klein, A., van IJcken, W. F. J., van den Akker, E., et al. (2024) · HemaSphere · doi:10.1002/hem3.139 · Cited by 5
Emerging drugs for the treatment of sickle cell disease: a review of phase II/III trials
Mercier‐Ross, J., Forté, S., & Soulières, D. (2022) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2022.2105835 · Cited by 5
“Other agents with HDAC inhibiting properties are trialed in phase I, including panobinostat (NCT01245179, still active) and pomalidomide (NCT01522547) which showed increased HbF levels in two of four patients [45].”
BackgroundHandgretinger, R., & Mezger, M. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2399134 · Cited by 7
“It was known that some individuals with hereditary persistence of fetal hemoglobin (HPFH) and SCD or TDT have few or no symptoms of the disease [11–13].”
Aygün, B., Bello, A. C., Thompson, A. A., et al. (2022) · American Journal of Hematology · doi:10.1002/ajh.26470 · Cited by 4
Pharmacogenomics of Hydroxyurea Therapy and Fetal Hemoglobin Levels in Sickle Cell Anemia
Sales, R. R., Nogueira, B. L., & Luizon, M. R. (2022) · Pharmacogenomics · doi:10.2217/pgs-2022-0050 · Cited by 4
Hara, Y., Kawabata, E., Lemgart, V. T., Bronson, P. G., Hicks, A., Peters, R., Krishnamoorthy, S., Ribeil, J., Schmunk, L. J., Eglinton, J., et al. (2023) · medRxiv · doi:10.1101/2023.03.14.23287244 · Cited by 4
Chakravorty, S., & Greenough, A. (2025) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2025.2551353 · Cited by 4
“Building on decades of evidence on the role of HbF in ameliorating SCD symptoms and mechanism of hemoglobin switch from HbF to HbA in infancy, sustained and homogeneous increase in HbF expression in erythroid precursors remains a valid therapeutic goal [73].”
Esrick, E. B., Lehmann, L., Federico, A., Vincon, H., Liu, B., Daley, H., Dansereau, C., Oliveira, S. D., Everett, J. K., Kao, P., et al. (2026) · Blood · doi:10.1182/blood.2026033871 · Cited by 3
Seck, M., Dabo, M. A., Bousso, E. S., et al. (2024) · Advances in Hematology · doi:10.1155/2024/7501577 · Cited by 3
“HbF levels have been shown in previous studies to be a protective factor against morbidity and mortality in SCD patients [14, 31].”
ResultTakezaki, M., Li, Y., Xu, H., Patel, N., Lucas, R., Cerbone, R. E., Koti, S., Hendrick, C. L., Junker, L. H., & Pace, B. S. (2025) · PLoS ONE · doi:10.1371/journal.pone.0323550 · Cited by 3
“Various classes of molecules increase HbF expression in tissue culture systems and preclinical animal models [17], however few have made it to clinical trials.”
Choi, J. W., Lee, M. H., & Fujii, T. (2021) · BioMed Research International · doi:10.1155/2021/8383875 · Cited by 3
Hara, Y., Lemgart, V. T., Halland, N., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022008710 · Cited by 3
Exome sequencing in high and low fetal haemoglobin Arab–Indian haplotype sickle cell disease
Al-Nafie, A. N., Al-Ateeq, S., Al‐Muhanna, F., Alsulaiman, A. M., Alfarhan, M. F. A., Buali, W., Vatte, C., Cyrus, C., Keating, B. J., Al‐Ali, A. K., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17542 · Cited by 3
“In 619 adult HbS homozygotes, mean HbF was 16 5 7 3%; in 137 additional Arab–Indian haplotype patients, HbF was <10% in the lowest quartile and >30% in the highest quartile of HbF distribution.(1,2) Among patients homozygous for Arab–Indian haplotype, the common minor alleles of BCL11A and MYB accounted for 4 2% to 8…”
BackgroundSelf-citationA one-base therapeutic insertion in the HBG2 distal promoter reactivates γ-globin expression
Bao, X., Gao, Y., Chen, X., Wang, Z., Feng, X., Wang, L., Du, J., Ye, Y., Chen, F., Du, L., et al. (2025) · Experimental Hematology and Oncology · doi:10.1186/s40164-025-00626-7 · Cited by 2
“Reactivating γ-globin or fetal hemoglobin (HbF, α2γ2) expression, which is silenced after birth, has been a promising therapeutic strategy for β-thalassemia and sickle cell disease [1–3].”
Arbai, K., Ismaili, F. Z. A., Zian, Z., et al. (2025) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-025-02102-y · Cited by 2
“Fetal hemoglobin (HbF) expression plays a crucial role in the variability of clinical manifestations in SCD, composed of two α and two γ chains, which predominate in fetuses and newborns [11].”
Cai, D., Chan, Y., He, G., Kong, Y., Cai, A., Guo, Y. P., & Zhu, B. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1578237 · Cited by 3
“HU has been demonstrated to increaseHbFlevels(Steinberg,2020)inbothK562cellsandadultErPCs (Zhu et al., 2014), and it is utilized in the treatment of β -thalassemia patients (Sales et al., 2021; Gambari et al., 2024).”
Adeagbo, B. A., Olarewaju, O. J., Orherhe, O. M., Chikwambi, Z., Mazhindu, A., Bolarinwa, R. A., Bolaji, O. O., & Masimirembwa, C. M. (2025) · Gates Open Research · doi:10.12688/gatesopenres.16370.1 · Cited by 3
Zhang, Q., Li, J., Huang, H., Shang, X., Ye, Y., Zhang, W., Lin, P., Gong, Y., Hoh, B., Luo, Q., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65019-0 · Cited by 2
“Early evidence emerged from studies on small groups of Africans with sickle cell anemia, where distinct β -globin locus haplotypes were linked to varying hematological traits 58 .”
Single-cell transcriptomics reveals heterocellular γ-globin gene expression in Aγδβ-thalassemia
Doerfler, P. A., Li, Y., Yao, Y., Feng, R., Mayuranathan, T., Zhang, J., Kooienga, E., Cullins, D. L., Jesudas, R., Williams, D. C., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016755 · Cited by 2
Goswami, S. G., Gupta, P., Arvinden, V. R., Bhargava, N., Iyer, A. R., Saravanakumar, V., Yadav, P., Jha, S. K., Singh, S., Kumar, A., et al. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04582-1 · Cited by 2
“Several studies have demonstrated that enhanced HbF production is linked to decreased morbidity and mortality in both SCD and BT [23–26].”
Genetics and Genomics in Sickle Cell Disease in Africa
Nkya, S. W., Makani, J., & Flanagan, J. M. (2026) · American Journal of Hematology · doi:10.1002/ajh.70220 · Cited by 5
Progrès de la thérapie génique dans les maladies génétiques du système hématopoïétique
Cavazzana, M. (2022) · médecine/sciences · doi:10.1051/medsci/2022120 · Cited by 2
Brahim, A. T., Taleb, M., Soumaré, H., Ghaber, S. M., Mohamed, A., & Boukhary, A. O. M. S. (2024) · Frontiers in Bioscience-Scholar · doi:10.31083/j.fbs1602011 · Cited by 3
Freire, A., Charola-Ramos, L., González-Guerra, E., Gonçalves, J., Rocha, V., Afreixo, V. M. A., Martínez‐Carretero, E., & Raya, J. M. (2024) · Anemia · doi:10.1155/2024/1687917 · Cited by 2
“…and hematological values, a signifcant association was verifed with Hb, RDW, HCM, and WBC. Patients with high levels of HbF had higher levels of Hb and HCM and reduced levels of RDW, refecting the reduction in the degree of 6 Anemia hemolysis due to the antipolymerization efect of HbF in SCA [47].”
BackgroundCYB5R3 T117S tempers fetal hemoglobin induction by hydroxyurea in patients with sickle cell disease
Chowdhury, F. A., Sharma, M., Schafer, D., Nouraie, M. S., Gladwin, M. T., Straub, A. C., & Wood, K. C. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024013801 · Cited by 2
Investigating the missing heritability of fetal haemoglobin level in Africa
Wonkam, A. (2020) · British Journal of Haematology · doi:10.1111/bjh.17101 · Cited by 2
“It is, therefore, not unreasonable to hypothesise that availability of appropriate GWAS arrays purposefully designed to capture African population genetic variations, similar to that being developed by the H3Africa consortium,22 could help in addressing the missing heritability of foetal haemoglo- bin in a desirably l…”
BackgroundSuwito, B. E., Adji, A. S., Widjaja, J. S., Angel, S. C. S., Hajiri, A. Z. Z. A., Salamy, N. F. W., & Choirotussanijjah, C. (2023) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2023.11435 · Cited by 3
RNA therapeutics for the treatment of blood disorders
Ngo, A. D., Nguyen, H. L., Çağlayan, Ş., & Chu, D. (2024) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2023.11.005 · Cited by 1
Une approche CRISPR/Cas pour traiter les β-hémoglobinopathies
Brusson, M., & Miccio, A. (2025) · médecine/sciences · doi:10.1051/medsci/2024191 · Cited by 2
Palani, C. D., Smith, A., Cao, X., Li, Y., Pace, B. S., & Starlard‐Davenport, A. (2025) · British Journal of Haematology · doi:10.1111/bjh.20107 · Cited by 1
The role of hemoglobin F in sickle cell disease complications: a descriptive secondary analysis
Aston, H. M., Price, E., Wernecke, E., Hazenberg, E., Herrera, D., Gollan, S., Xu, H., Raval, G. G., & Kutlar, A. (2025) · Blood Vessels Thrombosis & Hemostasis · doi:10.1016/j.bvth.2025.100114 · Cited by 2
Hara, Y., Lemgart, V. T., Lessard, S., Mercadante, C. J., Ribeil, J., Hicks, A., Rimmelé, P., & Light, D. R. (2025) · Science Advances · doi:10.1126/sciadv.adx1144 · Cited by 1
MAZ regulates fetal hemoglobin repression by activating MYB transcription
Lu, D., Yang, Y., Yang, B., Chen, D., Zhu, M., Huang, S., Hu, J., Zhu, L., Fan, W., Xie, Y., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-30733-8 · Cited by 1
“Key transcription factors such as MYB and BCL11A play pivotal roles in repressing γ-globin (HBG) genes expression in adults 13–16 , while factors like EHMT2, LYAR, WDR5, and PRMT1 contribute to the intricate regulatory network that governs globin gene expression 17–20 .”
A new advance in therapeutic induction of fetal hemoglobin on an uncertain road to durable access
Manwani, D. G., Capellera-Garcia, S., & Weiss, M. J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.12.030 · Cited by 1
Emerging Considerations in Transfusion Medicine
Gibson, N. M., Kwiatkowski, J. L., & Chou, S. T. (2025) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2025.10.006 · Cited by 1
Márquez-Benitez, Y., Osorio-Garzón, V. I., Bernal, J. E., & Briceño, I. (2026) · Genes · doi:10.3390/genes17020135 · Cited by 1
“This mechanism prevents γ globin gene silencing and increases HbF levels [21,22].”
Lopez, A., Gargano, M. A., Yang, H., Ogunsile, F. J., Li, N., Xie, Y., Jeyakumar, S., & Udeze, C. (2026) · Journal of Medical Economics · doi:10.1080/13696998.2026.2624971 · Cited by 2
Ten years of clinical genetic therapies for sickle cell disease: Current and future directions
Leonard, A. (2026) · Seminars in Hematology · doi:10.1053/j.seminhematol.2026.03.013 · Cited by 1
Targeting BCL11A through gene therapy in sickle cell disease: Will one size fit all or most?
Alsultan, A. S. (2024) · Pediatric Blood & Cancer · doi:10.1002/pbc.30934 · Cited by 1
“6 The effectiveness of BCL11A -based gene therapy in SCD patients with heritable reduced BCL11A expression and associated high levels of HbF who are seriously ill is currently unknown.”
BackgroundAvascular Bone Necrosis in Pediatric Patients with Sickle Cell Disease in Basrah, Iraq
Hamood, W. A., Hassan, M. K., & Yesser, W. J. (2024) · Journal of Applied Hematology · doi:10.4103/joah.joah_14_24 · Cited by 1
Impact of Foetal Haemoglobin on Disease Severity among Sickle Cell Subjects
Dogonzo, Y. I. (2024) · Haematology International Journal · doi:10.23880/hij-16000246 · Cited by 1
Manco, L., Morais, A. M., Almeida, S. M., Salgado, I., Relvas, L., Monteiro, C., Queiroz, G., & Bento, C. (2025) · Frontiers in Bioscience-Scholar · doi:10.31083/fbs38388 · Cited by 1
Nkya, S. W., Mahawi, I., Shungu, R., Nzunda, C., Kaywanga, F., Solomon, D., Kerrety, T., Josephat, E., Christopher, H., Ngowi, D., et al. (2025) · Annals of Hematology · doi:10.1007/s00277-025-06479-8 · Cited by 1
Sickle cell haemoglobin and its interactions with other variant haemoglobins and with thalassaemias
FRCPath, B. J. B. M. F., & Rees, D. C. (2024) · Wiley eBooks · doi:10.1002/9781394265381.ch4 · Cited by 1
CRISPR, ZFNS, and TALENS for Hemoglobinopathies an Analysis
Khare, V. (2021) · International Journal for Research in Applied Science and Engineering Technology · doi:10.22214/ijraset.2021.38924
Metadata
- Authors
- Steinberg, M. H.
- Affiliations
- Boston University (US)
- Corresponding author
- Steinberg, Martin H.
- ORCID
- Steinberg, Martin H.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-11-19
- Volume
- 136
- Issue
- 21
- Pages
- 2392-2400
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W4211089719
- Cited by
- 136
- References
- 135
- Citations by year
- 2026: 27 · 2025: 28 · 2024: 35 · 2023: 11 · 2022: 21 · 2021: 11 · 2020: 2
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Funders
- University of Dammam (SP 11/2011)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL133350, R01HL068970)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- fetal hemoglobin, sickle cell disease, quantitative trait loci, beta-globin gene haplotypes, cell therapy, genome editing, curative treatment, Middle Eastern populations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
