The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index; 2 of the 124 sources its claims cite were checked for support.
Clonal hematopoiesis in human aging and disease
Open accessAbstract
Cryptic signs of aging in our blood: Time is not a friend to our DNA. Aging is associated with an accumulation of somatic mutations in normal dividing cells, including the hematopoietic stem cells (HSCs) that give rise to all blood cells. Certain mutations in HSCs confer a fitness advantage that results in clonal expansions of mutant blood cells that sometimes—but not always—forecast the development of cancer and other age-related diseases. Jaiswal and Ebert review this process of “clonal hematopoiesis,” including the mechanisms by which it arises and the current state of knowledge regarding its effects on human health. Science , this issue p. eaan4673
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Clonal hematopoiesis, especially CHIP, is common with aging and driven largely by DNMT3A/TET2 mutations; it raises risk of blood cancers, cardiovascular disease, and mortality. Mouse and human data support causal roles in atherosclerosis and inflammation, though mechanisms and broader disease links remain uncertain.
Key findings
- Clonal hematopoiesis is age-related: detectable in <1% of healthy individuals under age 40 but 10–20% of those age 70 or older; in one study, a median of ~18% of blood cells carried the mutations. Nearly two-thirds of clonal hematopoiesis was accounted for by loss-of-function mutations in DNMT3A and TET2, with ASXL1 third most common.
- CHIP was associated with ~10-fold increased relative risk of hematological malignancies; 4% of CHIP carriers developed a blood cancer over 8 years, corresponding to ~0.5% conversion per year. Nested case-control studies found ~3- to 5-fold increased AML risk.
- CHIP was associated with a 30–40% increased mortality risk and increased cardiovascular risk: coronary heart disease and ischemic stroke risk more than doubled, early-onset MI risk was four times higher, and JAK2 mutations conferred ~12-fold higher coronary heart disease risk and ~12-fold venous thrombosis risk.
- Mouse models showed that Tet2 or Dnmt3a loss accelerates atherosclerosis and heart failure, with IL-1B blockade reversing accelerated atherosclerosis; CHIP genes also affect inflammatory pathways including IL6 and IL8.
Methods
- Narrative review; no primary data collection or formal meta-analysis.
- Synthesizes human population and exome sequencing studies, including cohorts of greater than 30,000 persons, nested case-control studies, and mouse models.
- Main analysis is qualitative synthesis of genetic associations, clinical outcomes, and mechanistic experiments.
Limitations
- Stated: mechanisms by which DNMT3A/TET2 and splicing factor mutations drive clonal expansion remain unclear; causality for non-malignant diseases beyond cardiovascular disease is not established, with type 2 diabetes possibly reflecting reverse causation and COPD potentially confounded by smoking.
- Stated: prevalence estimates depend heavily on detection sensitivity, and the biological significance of smaller clones is unknown; clone trajectories vary between people and risk stratification remains incomplete.
- Evident: as a narrative review, it lacks systematic search or quality assessment and provides no new primary data; risk estimates are drawn from heterogeneous studies.
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Claims the paper makes
79 Not checked yet · 26 Own interpretation · 20 No basis given · 5 Own result · 1 Partly supported · accuracy not yet measured
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In the paper
“also found that Il1b, IL8 family chemokines, and other inflammatory mediators show increased expression in Tet2-deficient macrophages challenged with low-density lipoprotein or endotoxin 79,86,92”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
What the sources say
- Supportedcites [79] Jaiswal S Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med 377, 111– 121, doi: 10.1056/NEJMoa1701719 (2017). 28636844 PMC6717509 source
The Results section reports increased Il1b and CXC chemokine transcripts in Tet2-deficient macrophages exposed to LDL, and greater secretion of inflammatory proteins after LDL loading or endotoxin exposure than in controls. It qualifies that endotoxin, but not LDL, caused robust Il1b secretion. (LLM, conf=0.90)
- Partly supportedcites [86] Fuster JJ Clonal hematopoiesis associated with Tet2 deficiency accelerates atherosclerosis development in mice. Science, doi: 10.1126/science.aag1381 (2017). PMC5542057 28104796 sourceExperimental — accuracy not yet measured
The paper’s Abstract reports increased Il1b expression and broader cytokine and chemokine expression in TET2-deficient macrophages treated with LPS/IFN-γ. But under oxLDL/TNF/IFN-γ stimulation, it says the effect on other cytokines and chemokines was minimized, with IL-1β the exception. The passages do not specifically identify IL8-family chemokines as increased, so the claim overgeneralizes across the two challenges. (LLM, conf=0.88)
- Not checked yetcites [92] Cull AH, Snetsinger B, Buckstein R, Wells RA & Rauh MJ Tet2 restrains inflammatory gene expression in macrophages. Exp Hematol 55, 56– 70 e13, doi: 10.1016/j.exphem.2017.08.001 (2017). 28826859 source
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- Supported
In the paper
“As each HSC acquires ~1 exonic mutation per decade of life 3,”
§ Clonal hematopoiesis in human aging and disease > Introduction
What the sources say
- Not checked yetcites [3] Welch JS The origin and evolution of mutations in acute myeloid leukemia. Cell 150, 264– 278, doi: 10.1016/j.cell.2012.06.023 (2012). 22817890 PMC3407563 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“But in the 1990s, studies of non-random X-chromosome inactivation (XCI) in women led to the discovery that clonal hematopoiesis also occurs in individuals without cancer 18.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [18] Fey MF Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe. Blood 83, 931– 938 (1994). 8111064 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The surprising result of this experiment of nature was that clonal hematopoiesis largely results from mutations in a very restricted set of genes.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This outgrowth, called “clonal hematopoiesis,” is highly prevalent in the elderly population.”
- Also stated in: § Introduction · boosted
“Indeed, numerous studies have now shown that such outgrowths of mutated blood cells, termed “clonal hematopoiesis,” are highly prevalent in the elderly.”
§ Clonal hematopoiesis in human aging and disease > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Introduction · boosted
In the paper
“Importantly, non-random XCI in blood cells was observed to increase in frequency with age, although the underlying mechanism was unclear 19.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [19] Champion KM, Gilbert JG, Asimakopoulos FA, Hinshelwood S & Green AR Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes. British journal of haematology 97, 920– 926 (1997). 9217198 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The third most commonly mutated gene was ASXL1, a chromatin regulator, while mutations in splicing factors (SF3B1, SRSF2, PRPF8, U2AF1) were also frequent.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This was the first demonstration that mutation-driven clonal hematopoiesis occurs in healthy persons 20.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [20] Busque L Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nature genetics 44, 1179– 1181, doi: 10.1038/ng.2413 (2012). 23001125 PMC3483435 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Like most cancers, AML generally results from several driver mutations that occur sequentially in the same clone over time 3.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [3] Welch JS The origin and evolution of mutations in acute myeloid leukemia. Cell 150, 264– 278, doi: 10.1016/j.cell.2012.06.023 (2012). 22817890 PMC3407563 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutations in classical oncogenes and tumor suppressors, such as those involved in cellular growth signaling (JAK2, GNAS, GNB1, CBL) and the DNA damage response (TP53, PPM1D), were seen but were not the most common.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 31
- Probably not a substantial claim. 18
None of the sources cited for this claim have been checked yet.
In the paper
“An equivalent state is also pervasive in the epithelium of skin 14 and esophagus 15,16, suggesting that somatic mutation-driven clonal expansions may be a characteristic of aging in several tissues.”
§ Clonal hematopoiesis in human aging and disease > Introduction
What the sources say
- Not checked yetcites [14] Martincorena I Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880– 886, doi: 10.1126/science.aaa6806 (2015). 25999502 PMC4471149 source
- Not checked yetcites [15] Martincorena I Somatic mutant clones colonize the human esophagus with age. Science 362, 911– 917, doi: 10.1126/science.aau3879 (2018). 30337457 PMC6298579 source
- Not checked yetcites [16] Yokoyama A Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565, 312– 317, doi: 10.1038/s41586-018-0811-x (2019). 30602793 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“by the age of 70 an average person would be expected to harbor up to 1.4 million protein-coding variants, corresponding to an average of 70 mutations per gene, in at least one HSC (Fig. 1).”
§ Clonal hematopoiesis in human aging and disease > Introduction
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In later studies, DNA sequencing of HSCs from AML patients in remission revealed that stem cells with only a single driver mutation were often present, suggesting that pre-malignant clonal hematopoiesis was a generalizable finding in AML 23–25.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [23] Jan M Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science translational medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012). PMC4045621 22932223 source
- Not checked yetcites [24] Shlush LI Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506, 328– 333, doi: 10.1038/nature13038 (2014). 24522528 PMC4991939 source
- Not checked yetcites [25] Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC & Majeti R Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A 111, 2548– 2553, doi: 10.1073/pnas.1324297111 (2014). 24550281 PMC3932921 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Aging is associated with a steady increase in the number of somatic mutations in virtually all tissues 1–5.”
§ Clonal hematopoiesis in human aging and disease > Introduction
What the sources say
- Not checked yetcites [1] Blokzijl FJ, Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538, 260 (2016). 27698416 PMC5536223 source
- Not checked yetcites [2] Hoang ML, Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing. Proc Natl Acad Sci U S A 113, 9846 (2016). 27528664 PMC5024639 source
- Not checked yetcites [3] Welch JS The origin and evolution of mutations in acute myeloid leukemia. Cell 150, 264– 278, doi: 10.1016/j.cell.2012.06.023 (2012). 22817890 PMC3407563 source
- Not checked yetcites [4] Martincorena I & Campbell PJ Somatic mutation in cancer and normal cells. Science 349, 1483– 1489, doi: 10.1126/science.aab4082 (2015). 26404825 source
- Not checked yetcites [5] Yizhak K, RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364, doi: 10.1126/science.aaw0726 (2019). PMC7350423 31171663 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Blood cancers such as chronic myeloid leukemia were first demonstrated to be clonal from karyotypic analysis and are the prototypical example of clonal hematopoiesis 17.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [17] Rowley JD Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290– 293 (1973). 4126434 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Somatic clones were detectable in less than 1% of healthy individuals under age 40, but they increased in frequency with each decade of life.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues.”
§ Clonal hematopoiesis in human aging and disease > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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In the paper
“Mouse models carrying loss-of-function mutations in either of these genes clearly show an HSC competitive advantage in vivo as well as a propensity for leukemia when cooperating mutations are present 50–53.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
What the sources say
- Not checked yetcites [50] Ko M Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci U S A 108, 14566– 14571, doi: 10.1073/pnas.1112317108 (2011). 21873190 PMC3167529 source
- Not checked yetcites [51] Challen GA Dnmt3a is essential for hematopoietic stem cell differentiation. Nature genetics 44, 23– 31, doi: 10.1038/ng.1009 (2012). PMC3637952 22138693 source
- Not checked yetcites [52] Guryanova OA DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat Med 22, 1488– 1495, doi: 10.1038/nm.4210 (2016). 27841873 PMC5359771 source
- Not checked yetcites [53] Cole CB Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies. J Clin Invest 127, 3657– 3674, doi: 10.1172/JCI93041 (2017). 28872462 PMC5617681 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“While the accumulation of both small and large somatic variants are linked to aging, the underlying biology of the two is generally non-overlapping.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“But large structural variation, such as gains or losses of large segments of chromosomes, also increases with age and has clinically meaningful associations 34–36.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
What the sources say
- Not checked yetcites [34] Bonnefond A Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications. Nature genetics 45, 1040– 1043, doi: 10.1038/ng.2700 (2013). 23852171 source
- Not checked yetcites [35] Jacobs KB Detectable clonal mosaicism and its relationship to aging and cancer. Nature genetics 44, 651– 658, doi: 10.1038/ng.2270 (2012). 22561519 PMC3372921 source
- Not checked yetcites [36] Loh PR Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 559, 350– 355, doi: 10.1038/s41586-018-0321-x (2018). 29995854 PMC6054542 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Stem cells from these mice are able to serially replate in colony forming assays over many generations, whereas wild-type stem cells quickly lose this capacity, suggestive of enhanced self-renewal capacity in the mutant stem cells 54,55.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
What the sources say
- Not checked yetcites [54] Moran-Crusio K Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer cell 20, 11– 24, doi: 10.1016/j.ccr.2011.06.001 (2011). 21723200 PMC3194039 source
- Not checked yetcites [55] Celik H Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic transformation. Blood 125, 619– 628, doi: 10.1182/blood-2014-08-594564 (2015). 25416276 PMC4304107 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In one study, 4% of CHIP carriers developed a blood cancer over the subsequent 8 years, corresponding to ~0.5% of CHIP cases converting to malignancy per year 28.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
What the sources say
- Not checked yetcites [28] Jaiswal S Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371, 2488– 2498, doi: 10.1056/NEJMoa1408617 (2014). 25426837 PMC4306669 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“For comparison, previously described mutations in the blood of healthy persons such as BCR-ABL or BCL2 translocations were usually present in less than 0.01% of cells and were often transient 29,30.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
What the sources say
- Not checked yetcites [29] Biernaux C, Loos M, Sels A, Huez G & Stryckmans P Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals. Blood 86, 3118– 3122 (1995). 7579406 source
- Not checked yetcites [30] Liu Y, Hernandez AM, Shibata D & Cortopassi GA BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci U S A 91, 8910– 8914 (1994). 8090743 PMC44716 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The PIGA gene is required for the synthesis of glycophosphotidylinositol (GPI) and its loss results in down-regulation of several cell surface proteins that are GPI anchored 60.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
What the sources say
- Not checked yetcites [60] Brodsky RA Paroxysmal nocturnal hemoglobinuria. Blood 124, 2804– 2811, doi: 10.1182/blood-2014-02-522128 (2014). 25237200 PMC4215311 source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Stochastic processes such as constriction of the stem cell pool with aging may also lead to clonal hematopoiesis in the absence of a known driver mutation.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis of indeterminate potential (CHIP)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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In the paper
“CHIP itself does not denote a malignancy, nor is it associated with clinically significant alterations in blood counts 28,63.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
What the sources say
- Not checked yetcites [28] Jaiswal S Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371, 2488– 2498, doi: 10.1056/NEJMoa1408617 (2014). 25426837 PMC4306669 source
- Not checked yetcites [63] Buscarlet M DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 130, 753– 762, doi: 10.1182/blood-2017-04-777029 (2017). 28655780 source
plain- Asserted: passes — The authors put it forward as true.
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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
“Loss of some of these proteins may allow for immune escape, thus explaining selection for PIGA-mutated clones.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, CHIP has been reported to be more common in older men 28 and smokers 27 and less common in Hispanics 28, although these associations are all relatively modest.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
What the sources say
- Not checked yetcites [28] Jaiswal S Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371, 2488– 2498, doi: 10.1056/NEJMoa1408617 (2014). 25426837 PMC4306669 source
- Not checked yetcites [27] Genovese G Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371, 2477– 2487, doi: 10.1056/NEJMoa1409405 (2014). 25426838 PMC4290021 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Subsequent studies showed that loss of Tet2 or Dnmt3a led to worsening heart function in a mouse model of congestive heart failure, corroborating the human genetic association 87,88.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [87] Sano S CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease. Circ Res 123, 335– 341, doi: 10.1161/CIRCRESAHA.118.313225 (2018). 29728415 PMC6054544 source
- Not checked yetcites [88] Sano S Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1beta/NLRP3 Inflammasome. J Am Coll Cardiol 71, 875– 886, doi: 10.1016/j.jacc.2017.12.037 (2018). 29471939 PMC5828038 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.
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
“These studies indicate that CHIP in the setting of other cancers is likely to be especially pervasive and portends a poor prognosis.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, JAK2 mutations prime neutrophils to form neutrophil extracellular traps, leading to thrombosis, which may also contribute to poor cardiovascular outcomes 82.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [82] Wolach O Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Science translational medicine 10, doi: 10.1126/scitranslmed.aan8292 (2018). PMC6442466 29643232 source
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.
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 CHIP also had increased mortality, most often due to progression of their primary malignancy.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- 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
“First, tissue architecture constrains the extent of clonal expansion within tissues such as gut or skin epithelium to patches that are rarely larger than a few square millimeters 15, but there is no such spatial restriction on HSCs, which freely admix throughout the bone marrow and body 78.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [15] Martincorena I Somatic mutant clones colonize the human esophagus with age. Science 362, 911– 917, doi: 10.1126/science.aau3879 (2018). 30337457 PMC6298579 source
- Not checked yetcites [78] Wright DE, Wagers AJ, Gulati AP, Johnson FL & Weissman IL Physiological migration of hematopoietic stem and progenitor cells. Science 294, 1933– 1936, doi: 10.1126/science.1064081 (2001). 11729320 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“Heart function in these studies was also improved with blockade of IL-1B, suggesting that this may be a common pathway for reversing the effects of CHIP in the heart.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
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.
It may state two separate claims as one.
In the paper
“this could represent a case of reverse causation, as hyperglycemia might influence the development or expansion of clones by interfering with TET2 function 90”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [90] Wu D Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559, 637– 641, doi: 10.1038/s41586-018-0350-5 (2018). 30022161 PMC6430198 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.
In the paper
“In addition, individuals with larger mutant clones had the greatest risk of cardiovascular disease, mirroring the situation for malignancy risk 79.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [79] Jaiswal S Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med 377, 111– 121, doi: 10.1056/NEJMoa1701719 (2017). 28636844 PMC6717509 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.
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
“In contrast to tissue-specific cells or epithelia, immune cells such as lymphocytes, granulocytes, and monocytes can migrate to and influence nearly every organ.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Myeloid malignancies were most common, although some people with CHIP did develop lymphoid cancers 27,28.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
What the sources say
- Not checked yetcites [27] Genovese G Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371, 2477– 2487, doi: 10.1056/NEJMoa1409405 (2014). 25426838 PMC4290021 source
- Not checked yetcites [28] Jaiswal S Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371, 2488– 2498, doi: 10.1056/NEJMoa1408617 (2014). 25426837 PMC4306669 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.
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
“Mutations in JAK2 have a well-described role in activating STAT transcription factors, which are central to immune response in several cell types involved in atherosclerosis.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
boosteddirect- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In a separate study (83), individuals with CHIP-associated JAK2 mutations were reported to have a ~12 times greater risk of developing venous thrombosis than those without CHIP, whereas individuals with mutations in other CHIP-associated genes had a doubling of the risk 82.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [82] Wolach O Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Science translational medicine 10, doi: 10.1126/scitranslmed.aan8292 (2018). PMC6442466 29643232 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Both groups found that loss of Tet2 in bone marrow cells led to an increase in the size of atherosclerotic lesions in hyperlipidemic mice, an effect that could not be explained by quantitative changes in blood cell parameters of the mutant mice 79,86.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [79] Jaiswal S Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med 377, 111– 121, doi: 10.1056/NEJMoa1701719 (2017). 28636844 PMC6717509 source
- Not checked yetcites [86] Fuster JJ Clonal hematopoiesis associated with Tet2 deficiency accelerates atherosclerosis development in mice. Science, doi: 10.1126/science.aag1381 (2017). PMC5542057 28104796 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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, CHIP was also strongly linked to smoking in these studies, so the result could be confounded by this association.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [37] Zink F Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 130, 742– 752, doi: 10.1182/blood-2017-02-769869 (2017). 28483762 PMC5553576 source
- Not checked yetcites [63] Buscarlet M DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 130, 753– 762, doi: 10.1182/blood-2017-04-777029 (2017). 28655780 source
hedgedcorrelational- 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
“Mechanistically, very little is known about why these specific gene expression changes are seen with loss of Dnmt3a.”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Some people have clones that remain stagnant in size for many years, whereas other people have clones that show steady growth 28,33.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
What the sources say
- Not checked yetcites [28] Jaiswal S Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371, 2488– 2498, doi: 10.1056/NEJMoa1408617 (2014). 25426837 PMC4306669 source
- Not checked yetcites [33] Young AL, Challen GA, Birmann BM & Druley TE Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nat Commun 7, 12484, doi: 10.1038/ncomms12484 (2016). 27546487 PMC4996934 source
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
“Understanding the causes and consequences of clonal hematopoiesis may provide a framework to understand this process, and aging, more broadly.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper may give no reason why it holds.
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
“It is also uncertain why some people have apparent clonal hematopoiesis in the absence of a known driver mutation.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“It is associated with blood cancers, cardiovascular disease, and overall mortality.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: 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.
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
“It is striking that the two most commonly mutated genes in CHIP, DNMT3A and TET2, are opposing enzymes in DNA methylation, yet both lead to convergent phenotypes in stem cell biology and immunity.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“The mechanisms by which the CHIP-associated mutations cause clonal expansion and enhanced inflammation is also a central unanswered question.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Bone marrow transplant recipients with hematological malignancies who received donor marrow from carriers of CHIP had higher rates of graft-versus-host disease and reduced relapse rates 95.”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
What the sources say
- Not checked yetcites [95] Frick M Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol, JCO2018792184, doi: 10.1200/JCO.2018.79.2184 (2018). 30403573 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.
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
“The process of mutation and clonal selection is likely to be universal across all organs and tissues.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“The changes in expression are relatively modest for each gene (~2 to 3-fold increase) but appear to be biologically significant given the number of genes that are dysregulated and the breadth of phenotypes seen in Tet2 knockout mice.”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
hedgedcorrelational- 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
“One possible explanation for this finding is that the donor cells harboring the mutations were capable of mounting stronger immune responses against both normal host tissues and the tumor.”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
What the sources say
- Not checked yetcites [95] Frick M Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol, JCO2018792184, doi: 10.1200/JCO.2018.79.2184 (2018). 30403573 source
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.
Probably not a substantial 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
“Furthermore, the interaction of CHIP with other risk factors, such as having type 2 diabetes or elevated serum levels of C-reactive protein, may be synergistic for adverse outcomes.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“It is likely that cell extrinsic factors, like the microenvironment, the microbiome, or diet, will play a role.”
§ Clonal hematopoiesis in human aging and disease > Future outlook
hedgedconditional- 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: fails — The paper may give no 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. The paper may give no reason why it holds.
The authors state this as an assumption.
Given a sufficiently large population, every possible mutation that can occur will occur in some HSCs.
“These studies can be thought of as a natural experiment of saturation mutagenesis in humans, and can be summarized in a simple postulate—given a sufficiently large population, every possible mutation that can occur will occur in some HSCs.”
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
“as CHIP mutations are known to increase the fitness of HSCs and myeloid progenitors5”
From Clonal hematopoiesis is associated with protection from Alzheimer’s disease (2023) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Most large-population-based studies define CHIP using a VAF threshold of ≥2%, reflecting the lower limit of reliable detection in standard whole-exome sequencing pipelines [2,32].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [32]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The prevalence of CHIP increases sharply with age, creating a significant biological intersection between individuals at risk for CHIP and late-onset AD [9,32].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“Examples include the possible links between clonal haematopoiesis and cardiovascular disease54; between mutations in liver disease and insulin resistance55; and between driver mutations in cavernomas and brain haemorrhages49,53,56.”
From Somatic mutation rates scale with lifespan across mammals (2022) · cites this paper as [56]
In the citing paper
“In humans, this manifests itself as ‘clonal haematopoiesis’, where one or a few HSC clones disproportionately contribute to blood production over time48,49.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
“In a separate study (83), individuals with CHIP-associated JAK2 mutations were reported to have a ~12 times greater risk of developing venous thrombosis than those without CHIP”
§ Clonal hematopoiesis in human aging and disease > References
“83. Patel KV, Ferrucci L, Ershler WB, Longo DL & Guralnik JM Red blood cell distribution width and the risk of death in middle-aged and older adults.”
Citations
Cites
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738 · cited 1×
“If the first mutation to be acquired leads to clonal expansion without malignant transformation, it should be possible to identify a premalignant stage in which only the initiating lesion is present (22).”
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078 · cited 16×
“M. A. Sanders et al., MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML.”
BackgroundInfluentialAge-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · cited 9×
“Indeed, some individuals with clonal hematopoiesis have nearly all of their blood cells arising from a single mutated HSC (29).”
BackgroundInfluentialSelf-citationROWLEY, J. D. (1973) · Nature · doi:10.1038/243290a0 · Cited by 4,291 · cited 1×
“Blood cancers such as chronic myeloid leukemia were first demonstrated to be clonal from karyotypic analysis and are the prototypical example of clonal hematopoiesis (18).”
BackgroundChronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · cited 1×
“Growing evidence thus supports a role for the commonlymutatedCHIP genes in immune function, and CHIP may underlie some part of the phenomenon termed “inflammaging,” the age-associated increase in systemic inflammation (98).”
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Kralovics, R., Passamonti, F., Buser, A. S., Teo, S.-S., Tiedt, R., Passweg, J. R., Tichelli, A., Cazzola, M., & Skoda, R. C. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051113 · Cited by 3,470 · cited 1×
“Activating mutations in JAK2 allow constitutive signaling though growth factor receptors, thus leading to clonal expansion by enhanced proliferation of cells that carry this mutation (46).”
BackgroundTet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., & Zhang, Y. (2011) · Science · doi:10.1126/science.1210597 · Cited by 3,451 · cited 1×
“TET2 is one of three enzymes responsible for catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and further intermediates, which can eventually lead to demethylation (49, 50).”
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095 · cited 1×
“Like several other welldescribed markers in blood cells, such as red cell distributionwidth (84), DNAmethylation clocks (85), and loss of Y chromosome (86), CHIP is associated with multiple adverse outcomes in epidemiological studies.”
Cited by
Sorted by citations
Items 701–800 of 1,000
Tian, S., Jenkinson, G., Ferrer, A., Yan, H., Morales‐Rosado, J. A., Wang, K. L., Lasho, T. L., Yan, B. B., Baheti, S., Olson, J. E., et al. (2025) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf040 · Cited by 3
Tan, Y., Zhu, X., Huang, Y., Zhao, C., Cheng, X., Li, J., Zhang, G., Ma, T., Yang, S., & Bai, Y. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.322630 · Cited by 3
Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation
Leesang, T. E., Brabson, J. P., Yap, Y. S., Barbieri, D. A., Klimas, A. S., Pinzone, J., Ahearn, E. L., Lam, M. Q., Lyon, P. D., Swirski, A., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116379 · Cited by 3
“…cancers and imparts HSPCs with a competitive advantage, as seen in individuals with clonal hematopoiesis of indeterminate potential (CHIP), 81 future studies should explore the potential to combine ATRA and ascorbate treatment for the suppression of pre-malignant TET2-mutant hematopoiesis.”
Chronic inflammation and cancer: ASCO 2025 update
Dosser, C., Wolf, D. G. F., & Zimmer, K. (2025) · memo - Magazine of European Medical Oncology · doi:10.1007/s12254-025-01077-w · Cited by 3
“Beyond its established epidemiological association with cardiovascular diseases and hematologic malignancies, CH is now understood to be an imprint of a pro-inflammatory phenotype on peripheral immune cells, thereby acting as a systemic mediator of chronic inflammation [21, 22].”
Cell cycle criticality as a mechanism for robust cell population control
Simons, B. D., & Karin, O. (2025) · Molecular Systems Biology · doi:10.1038/s44320-025-00164-8 · Cited by 3
“One system where clonal dynamics have been characterized during ageing is the blood, where a few clones with speci fi c mutations accumulate during ageing, in a phenomenon known as clonal haematopoiesis (Jaiswal and Ebert, 2019).”
Reconstructing the lifelong history of cells and tissues via somatic mutation analysis
Faienza, S., Margaria, J. P., & Franco, I. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05946-9 · Cited by 4
“Clonal expansion driven by selection ubiquitously occurs in adult tissues, particularly the blood, and impacts physiological processes as well as age-related phenotypes [19, 26].”
Loss of Y chromosome in Alzheimer’s patients co-occurs with somatic mutations beyond CHIP drivers
Rychlicka-Buniowska, E., Sarkisyan, D., Horbacz, M., Bruhn‐Olszewska, B., Drężek-Chyła, K., Koszyński, M., Davies, H., Juhas, U., Wójcik, M., Klich‐Rączka, A., et al. (2025) · Life Science Alliance · doi:10.26508/lsa.202503533 · Cited by 3
“…an accumulation of post-zygotic (somatic) mutations, particularly in hematopoietic stem cells (HSCs), which are estimated to acquire up to 0.858 exonic mutations per year, summing up to about 1.4 million protein-coding mutations in a 70-yr-old individual (Welch et al, 2012; Jaiswal & Ebert, 2019).”
InfluentialNadar, S., Dohadwala, T. K., Kumaresan, N., Ahamed, S. I., & Fatima, S. (2025) · Clinical Hematology International · doi:10.46989/001c.146275 · Cited by 5
Midena, F., Alessandrini, L., Conci, C., Barcella, M., Gazzo, F., Jacchetti, E., Carsana, E., Benedicenti, F., Vacca, R., della Volpe, L., et al. (2026) · Cell stem cell · doi:10.1016/j.stem.2025.12.016 · Cited by 4
Obrębski, T., Maleszewska, M., Dunin-Horkawicz, S., & Malik, A. R. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111267 · Cited by 5
“In brief, mutations present in HSCs result in increased proliferation and self-renewal capacity, causing over-representation of mutated effector cells like monocytes, leukocytes, and neutrophils in the blood (81).”
Malkots, B., Stamatiou, I., Panagiotopoulos, E., Inglezou, L., Sakka, V., Vrachiolias, G., Misidou, C., Spanoudakis, E., Kotsianidis, Ι., & Liapis, K. (2026) · Cancers · doi:10.3390/cancers18091326 · Cited by 3
“In some cases, a mutation may offer a survival-growth advantage to the cell, leading to clonal expansion and clonal hematopoiesis [2,7].”
InfluentialAtherosclerotic Cardiovascular Disease and Cancer
Amend, A., Horstmann, H., Lavine, K. J., Giannarelli, C., & Moore, K. J. (2026) · Immunological Reviews · doi:10.1111/imr.70141 · Cited by 3
Clonal hematopoiesis, inflammation, and cardiovascular disorders: a mitochondrial connection
Pileri, F., & Natoli, G. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.07.009 · Cited by 3
Efficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang, Y., Fasching, L., Bae, T., Tomasini, L., Schreiner, J. D., Szekely, A. M., Fernandez, T. V., Leckman, J. F., Vaccarino, F. M., & Abyzov, A. S. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad254 · Cited by 3
“However, in aging individuals, where clonal hematopoiesis is highly prevalent (14), one would likely have a high degree of clone redundancy and the proposed strategy would be applicable, as it is applicable for analyzing clones in hematologic malignancies.”
BackgroundAge-related disease: Immune system
de Punder, K., & Karabatsiakis, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00004-9 · Cited by 3
Clonal hematopoiesis JAKs up plaque formation
Campbell, K., & Li, Q. Y. (2025) · Journal of Clinical Investigation · doi:10.1172/jci187529 · Cited by 3
Ragaini, S., Gallì, A., Genuardi, E., Gandossini, M., Alessandria, B., Civita, A. M., Evangelista, A., Amaducci, E., Stefoni, V., Cavallo, F., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2024014948 · Cited by 3
Revolutionising Cardio-Oncology Care with Precision Genomics
Chong, J. H., Chuah, C. T. H., & Lee, C. G. L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052052 · Cited by 5
“The 2% VAF threshold for defining CHIP was originally based on the technical sensitivity of exome sequencing [28,35].”
Qiu, F., Shao, W., Qin, X., Xu, R., & Lu, H. (2025) · Scientific Reports · doi:10.1038/s41598-025-87040-5 · Cited by 3
The physiological functions of ascorbate in the development of cancer
Agathocleous, M. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.052201 · Cited by 4
“These mutations are also present in clonally expanded hematopoietic stem cells (HSCs) and blood cells of older individuals, and predispose individuals to AML development (Jaiswal and Ebert, 2019).”
Ye, X., Yang, X. Z., Carbone, R., Barshack, I., & Katz, R. L. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.97631 · Cited by 3
Mo, X., Zhou, M., Yan, H. M., Chen, X., & Wang, Y. (2021) · Cancer Medicine · doi:10.1002/cam4.4087 · Cited by 3
Chronic Myelomonocytic Leukemia Gold Jubilee
Solary, É., & Itzykson, R. (2021) · Hemato · doi:10.3390/hemato2030026 · Cited by 3
“In all these conditions, the variant allele frequency of somatic mutations is much higher than that observed in healthy subjects with CHIP/ARCH [58].”
BackgroundSteensma, D. P. (2021) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2021.101327 · Cited by 3
Dave, J. M., Saito, J., Mottola, G., & Greif, D. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822546-2.00015-0 · Cited by 3
Stolzenbach, V., Woods, D. C., & Tilly, J. L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.942652 · Cited by 3
“Before the age of 40, somatic clones are nearly undetectable, being found in less than 1% of individuals; however, this frequency increases dramatically as humans age (Jaiswal and Ebert, 2019).”
BackgroundInfluentialThe etiology of clonal mosaicism in human aging and disease
Massaar, S., & Sanders, M. A. (2023) · Aging and Cancer · doi:10.1002/aac2.12061 · Cited by 4
Balla, B., Tripon, F., Cândea, M., & Bănescu, C. V. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13081239 · Cited by 3
“to clonal hematopoiesis if it occurs in the hematopoietic system [51].”
BackgroundInfluentialClonal hematopoiesis of indeterminate potential: implications for the cardiologists
Sciatti, E., D’Elia, E., Gori, M., Grosu, A., Balestrieri, G., Senni, M., Barbui, T., & Gavazzi, A. (2023) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000001520 · Cited by 3
Single-cell genomics-based immune and disease monitoring in blood malignancies
Rathgeber, A. C., Ludwig, L. S., & Penter, L. (2024) · Clinical Hematology International · doi:10.46989/001c.117961 · Cited by 4
Body‐wide chimerism and mosaicism are predominant causes of naturally occurring ABO discrepancies
Dauber, E. M., Haas, O. A., Nebral, K., Gassner, C., Haslinger, S., Geyeregger, R., Hustinx, H., Crottet, S. L., Scharberg, E. A., Müller‐Steinhardt, M., et al. (2024) · British Journal of Haematology · doi:10.1111/bjh.19618 · Cited by 3
“21,47,49,53,55 This notion seems to be clearly vindicated by the high numbers of myeloid malignancies that are seen in individuals with a haematopoiesis-restricted form of Rh mosaicism, 12,56 which however does not preclude that this can also result from an ascertainment bias.”
Evolution of myeloproliferative neoplasms from normal blood stem cells
Hormoz, S., Sankaran, V. G., & Mullally, A. (2024) · Haematologica · doi:10.3324/haematol.2023.283951 · Cited by 3
“28,29 These studies showed that certain somatic mutations occur at high frequencies across healthy individuals and that these frequencies increase with age.”
Higher risk profile among patients with TET2-mutated giant cell arteritis: a cluster analysis
Guédon, A. F., Ouafdi, A., Belfeki, N., Dellal, A., Ghriss, N., Scheen, M., Haidar, F., Espitia, O., Scoazec, J., Fain, O., et al. (2024) · RMD Open · doi:10.1136/rmdopen-2024-004694 · Cited by 3
“Further research is needed to better determine the cardiovascular prognosis and response to biotherapy in these patients.”
The role of genetic/epigenetic factors and microenvironment in hematopoietic stem cell ageing
Niazi, V., Parseh, B., & Ghafouri‐Fard, S. (2025) · Biogerontology · doi:10.1007/s10522-025-10218-x · Cited by 3
“Although it was traditionally believed that aged HSCs have low self-renewal capacity, several works suggest that outside of a transplant setting, some HSCs are highly capable of self-renewal (Beer-man et al. 2010; Jaiswal and Ebert 2019; Pang et al. 2011).”
Risk of clonal hematopoiesis in families exposed to radiation following the Chornobyl accident
Machiela, M. J., Wong, W. S. W., Mai, Z., Karyadi, D. M., Drozdovitch, V., Chan, I. C. C., Vij, V., Zhou, W., Luo, W., Wu, D., et al. (2025) · Carcinogenesis · doi:10.1093/carcin/bgaf056 · Cited by 4
“Potential intermediate effects of radiation exposure could be detectable as clonally expanded somatic mutations in circulating leukocytes, referred to as clonal hematopoiesis (CH) [5], which has been used to identify individuals at elevated leukemia risk.”
Infection makes micro-CHIPs into macro-CHIPs
Gopakumar, J., & Jaiswal, S. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.07.006 · Cited by 3
Self-citationSoil and Seed: Coconspirators in Therapy-Induced Myeloid Neoplasms
Shannon, K., & Link, D. C. (2020) · Blood Cancer Discovery · doi:10.1158/2643-3249.bcd-20-0080 · Cited by 3
Sowing the Seeds of Clonal Hematopoiesis
Liggett, L. A., Voit, R. A., & Sankaran, V. G. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.07.011 · Cited by 2
Genetic and non-genetic mechanisms of inflammation may promote transformation in leukemia
Vyas, P. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.01.006 · Cited by 3
Antherieu, G., Heiblig, M., Freyer, G., Ghesquières, H., & Falandry, C. (2023) · Drugs & Aging · doi:10.1007/s40266-023-01023-7 · Cited by 3
“First, the overall HSC pool is well known to decrease with age, leading to greater sensitivity to medullar treatment toxicity [23].”
BackgroundVascular medicine and cardio-oncology – A new, evolving clinical frontier
Versmissen, J., Power, J. R., & Moslehi, J. J. (2020) · Vascular Medicine · doi:10.1177/1358863x20910786 · Cited by 5
Karpova, D., Encabo, H. H., Donato, E., Kotova, I., Calderazzo, S., Leppä, A., Panten, J., Przbylla, A., Seifried, E., Kopp‐Schneider, A., et al. (2022) · medRxiv · doi:10.1101/2022.07.24.22277825 · Cited by 3
Chung, A., Guo, J., Wang, Y., Jia, Y., Corbitt, N., Li, L., Wei, Y., Zhu, M., Wang, Z., Guo, H., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.10.575013 · Cited by 3
Lee, Y., Tseng, H., & Yang, J. D. (2024) · Hepatology · doi:10.1097/hep.0000000000000898 · Cited by 3
Exploring haematopoietic stem cell dynamics through mitochondrial mutation profiling
Xia, Y., Chen, R., & Duan, S. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00190-2 · Cited by 3
Kirmani, S., Huan, T., Amburg, J. C. V., Joehanes, R., Uddin, M. M., Nguyen, N. Q., Yu, B., Brody, J. A., Fornage, M., Bressler, J., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4656898/v1 · Cited by 3
Mechanisms of Germline Stem Cell Competition across Species
Hodge, R. A., & Bach, E. A. (2024) · Life · doi:10.3390/life14101251 · Cited by 4
“Mutations in ASXL1 (encoding a chromatin regulator), SF3B1, SRSF2, PRPF8, and U2AF1 (encoding splicing factors), as well as mutations in oncogenes and tumor suppressors, were also observed [143] (Table 1).”
BackgroundUnwrapping stemness to revive T cells
Tsui, C., & Kallies, A. (2024) · Science · doi:10.1126/science.ads6217 · Cited by 3
Corty, R. W., Pershad, Y., Vlasschaert, C., Luo, L. Y., Mack, T., Amancherla, K. V., Robinson‐Cohen, C., Savona, M. R., & Bick, A. G. (2025) · medRxiv · doi:10.1101/2025.08.11.25333294 · Cited by 3
Li, M., Xie, S., Hou, T., Shao, T., Kuang, J., Liu, C., Qu, Y., Lu, C., Liu, J., Liu, X., et al. (2023) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3125 · Cited by 2
“38,39 To suppress these benign mutant backgrounds in the Enricher-v1 panel, we designed an in silico - based Filter by data mining the noisy mutations from both WBC and cfDNA sequencing information of a large population of healthy individuals.”
MethodClonal hematopoiesis of indeterminate potential and heart failure
Lyasnikova, E. A., Ivanchenko, L. Y., Козлова, С. Н., Sitnikova, M. Y., Kostareva, A. A., & Shlyakhto, E. V. (2024) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2024-6016 · Cited by 3
Epistemic limitations of measurable residual disease in haematological malignancies
Chin-Yee, B. H., Laplane, L., & Sujobert, P. (2025) · The Lancet Haematology · doi:10.1016/s2352-3026(25)00002-x · Cited by 2
The phenomenon of clonal hematopoiesis: etiology, classification and its prognostic role
Kunevich, E. O., Mikhaleva, M., Крысюк, О. Б., Bogdanov, A. N., Zherniakova, A., & Волошин, С. В. (2025) · Oncohematology · doi:10.17650/1818-8346-2025-20-1-28-54 · Cited by 2
Xu, H., Ma, M., Chen, L., Wang, C., & Asir, L. M. M. (2025) · Journal of Information Science · doi:10.1177/01655515251330617 · Cited by 2
Impact of Clonal Hematopoiesis on Solid Tumor Progression Following Radiation Therapy
Tao, J. J., Setton, J. S., Vela, P. S., Safonov, A. M., Comen, E. A., Braunstein, L. Z., Reis-Filho, J. S., Riaz, N., Powell, S. N., Levine, R. L., et al. (2025) · JCO Precision Oncology · doi:10.1200/po-24-00548 · Cited by 4
Chen, Y., Li, X., Zhao, S., Zhang, Y., Wang, H., Na, F., Guan, Q., Li, Z., Li, H., & Zhao, M. (2025) · The EPMA Journal · doi:10.1007/s13167-025-00413-8 · Cited by 2
“For example, age-related clonal hematopoiesis (CHIP) can significantly interfere with ctDNA testing, leading to false positives [90–92].”
Clonal hematopoiesis in AML long‐term survivors: Risk factors and clinical consequences
Krauß, S. M., Telzerow, E., Richter, D., Moret, A. S., Rothenberg‐Thurley, M., Sauerland, C., Weigert, A., Fraccaroli, A., Tischer, J., Ziemann, F., et al. (2025) · HemaSphere · doi:10.1002/hem3.70183 · Cited by 2
Kristiansen, M. H., Skov, V., Larsen, M. K., Kjær, L., Nielsen, C. H., Hasselbalch, H. C., & Wienecke, T. (2025) · British Journal of Haematology · doi:10.1111/bjh.20242 · Cited by 2
“7 With advancements in sensitive detection methods, even mutations present at very low variant allele frequencies (VAF) are now detectable.”
Liu, M., Zhou, L., Liu, Q., Wang, X., Wei, H., & Liu, Q. (2025) · HemaSphere · doi:10.1002/hem3.70187 · Cited by 2
Schmid, C. N., Sponagel, K., Bacher, U., Seipel, K., Porret, N. A., Wiedemann, G., Hoffmann, M., Daskalakis, M., & Pabst, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168021 · Cited by 4
“Also, the risk of developing a secondary myeloid neoplasm after treatment of solid tumors or lymphomas is increased [3,7–9].”
Zheng, B. J., He, J., Hu, W., Cao, Q., & Li, R. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189442 · Cited by 2
Tsirigotis, P. D., & Λαζανά, Ι. (2025) · Bone Marrow Transplantation · doi:10.1038/s41409-025-02725-9 · Cited by 2
“As more cases emerge, collaborative registries and further research are essential to guide early”
Zhang, Q., Wang, G., Yan, Z., Xu, W., Zhang, S., Li, J., Liang, L., Sun, C., Tang, R., Pircher, J., et al. (2025) · Heart Rhythm O2 · doi:10.1016/j.hroo.2025.09.024 · Cited by 2
“10,13 14–18 CHIP is recognized as being linked to cardiovascular illnesses, including CAD and heart failure.”
The Link Between Vitamins and Hematopoiesis: A Stem Cell Perspective
Gonçalves, C. E. D. S., Santos, A. A., Sartori, T., da Silva, R. O., Vivian, G. K., de Matos, L. A., Neves, B. R. O., Casagrande, J. G., Fock, R. A., & Hastreiter, A. A. (2025) · Stem Cells and Development · doi:10.1177/15473287251400298 · Cited by 2
“59 In this way, Chen et al. 58 describe serum vitamin C levels as being a marker that could pave the way toward the prevention against clonal hematopoiesis guided by molecular signatures.”
Of Barriers and Loops—How Evolution Limits Most Cancer Risks to Older Ages
Dominici, M. D., & DeGregori, J. V. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-0779 · Cited by 3
Blood-based epigenetic instability linked to human aging and disease
Basrai, S., Nofech-Mozes, I., Detroja, R., Scolari, F. L., Bakhtiari, M., Arruda, A., Murphy, T., Bratman, S. V., Chan, S. M., Minden, M. D., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-69430-z · Cited by 4
“Sites with low β -values were classi fi ed as unmethylated ESLs ( n = 31,744, Supplementary Data 2), and those with high β -values as methylated ESLs ( n =6143).”
The interplay of clonal hematopoiesis and cancer: Clinical implications in oncology
Tanguay, M., Tagliamento, M., Samaniego, J., Besse, B., Renneville, A., Bernard, E., & Micol, J. (2026) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2026.103109 · Cited by 3
Yuan, Q., & Guryanova, O. A. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-4497 · Cited by 2
Clonal haematopoiesis of indeterminate potential and risk of incident psychiatric disorders
Yu, Y., Wan, C., Li, J., Sun, Y., Yu, B., Tan, X., Wang, B., Lu, Y., & Wang, N. (2026) · BMC Medicine · doi:10.1186/s12916-026-04720-3 · Cited by 2
“Clonal haematopoiesis of indeterminate potential (CHIP) refers to the presence of clonal cells in the haematopoietic system of an apparently healthy individual, usually caused by mutations of driver genes in the haematopoietic system [4].”
Lipid nanoparticles for bone marrow-targeted RNA therapeutics
Casimiro, L. D. M., Escudero, R., Plessis, M. D., Schiffelers, R. M., & Heidenreich, O. T. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04423-0 · Cited by 2
The Evolution of Polyclonal Competition in Aging Hematopoiesis
Père, N. V. M., Terenzi, F., & Werner, B. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-0990 · Cited by 8
“Low-grade inflammation is a key associate to aging (62) and can be driven by various CH variants (14).”
Age-related decline in niche self-renewal factors drives testis aging via Hairless, Imp, and Chinmo
Chiang, P.-K., Lee, Y., Zheng, Y., Peng, C.-F., Wang, Y., Chang, S.-L., Hsu, H., Hsu, L., Bailetti, A. A., Bach, E. A., et al. (2026) · Science Advances · doi:10.1126/sciadv.adz0450 · Cited by 2
No evidence of immunosurveillance in mutation-hotspot-driven clonal hematopoiesis
Walkowiak, B., MacGregor, H. A. J., & Blundell, J. R. (2026) · Nature Genetics · doi:10.1038/s41588-026-02594-y · Cited by 4
Shen, Y., Boddul, S. V., Li, Z., Kasza, Z., Schülein, M., Raposo, B., Chemin, K., Jakobsson, P. ‐., Espinosa, A., Klareskog, L., et al. (2026) · Arthritis & Rheumatology · doi:10.1002/art.70267 · Cited by 2
Immune aging biomarkers for clinical trials
Cipriano, A., Justice, J. N., Poganik, J. R., Moqri, M., Abudayyeh, O. O., Gootenberg, J. S., Haynes, L., Levin, Y., Martin-Herranz, D. E., Akbar, A. N., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04493-5 · Cited by 3
“CHIP is common in aging and is associated with increased risk of cardiovascular disease and hematologic cancers 26 , although with reduced risk of some conditions such as Alzheimer’s disease 27 .”
Myelodysplastic Syndromes: 2026 Update on Diagnosis, Risk‐Stratification and Management
Garcia‐Manero, G. (2026) · American Journal of Hematology · doi:10.1002/ajh.70405 · Cited by 4
“Further adding importance to this concept is the discovery of the relation between comorbidities and clonal hematopoiesis [9] and MDS [10] suggesting an interplay between MDS and the development of other conditions such as cardiovascular disease [11].”
Liapis, K., Papadopoulos, V., Stamatiou, I., Koparanis, D., Inglezou, L., Panagiotopoulos, E., Malkots, B., Vrachiolias, G., Spyropoulos, T., & Kotsianidis, Ι. (2026) · Cancer · doi:10.1002/cncr.70531 · Cited by 2
“3,4 Much of this burden is coronary artery disease (CAD), which is increased between two and four times over the prevailing population rates.”
Nature of spontaneously arising single base substitutions in normal cells
Takeda, S., & Luan, Y. (2021) · Genome Instability & Disease · doi:10.1007/s42764-021-00056-9 · Cited by 2
“…et al., 2019), ulcerative colitis tissue (Kakiuchi & Ogawa, 2021; Kakiuchi et al., 2020), hematopoietic cells (Collins et al., 2020; Jacobs et al., 2012; Jaiswal & Ebert, 2019; Karczewski et al., 2020; Saiki et al., 2021), bronchi (Yoshida et al., 2020), and urinary bladder (Lawson et al., 2020;…”
Factors associated with clonal hematopoiesis and interaction with marrow environment
Nannya, Y. (2022) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-022-01380-0 · Cited by 2
“A Prevalence of CH depends on the scope of search and sequencing methods [9].”
BackgroundDiagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms
Morishita, S., & Komatsu, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241613008 · Cited by 3
“CHIP/ARCH individuals also have an increased risk of developing hematologic malignancies or cardiovascular diseases in patients with additional mutations [68].”
BackgroundUnveiling aging dynamics in the hematopoietic system insights from single-cell technologies
Jin, X., Zhang, R., Fu, Y., Zhu, Q., Hong, L., Wu, A., & Wang, H. (2024) · Briefings in Functional Genomics · doi:10.1093/bfgp/elae019 · Cited by 2
Ghanem, E. N. B. (2024) · Journal of Clinical Investigation · doi:10.1172/jci181064 · Cited by 2
“Since DNA methylation increases chromatin condensation, it is not surprising that loss of Tet2 , which demethylates DNA, would result in smaller, more compact NETs.”
BackgroundInfluentialHigh Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression
Resar, L. M. S., & Luo, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052125 · Cited by 2
“In support of this idea, hematopoietic stem cell (HSC) frequency increases with age, and concurrently, HSCs acquire somatic mutations with each cell division [17–28].”
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Delineating Mpl-dependent and -independent phenotypes of Jak2 V617F–positive MPNs in vivo
Papadopoulos, N., Nédélec, A., Rahmani, Y., Ryou, H., Defour, J., Rittscher, J., Royston, D. J., & Constantinescu, S. N. (2025) · Blood · doi:10.1182/blood.2024026711 · Cited by 2
Fighting aging-associated clonal hematopoiesis with microbial metabolite
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Therapy Response and Outcome Explained by Leukemia Cell of Origin
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“Mutations observed in CHIP frequently involve epigenetic regulators, the main ones being DNMT3A , TET2 and ASXL1 (Table 1) [3] .”
Clonal Hematopoiesis of Indeterminate Potential: New Insights from Recent Studies
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“This process represents the clonal hematopoiesis phenomenon observed in elderly human populations caused by a mutation selection process [17].”
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“Besides germline gene variants, acquired somatic mutations should be considered as well, especially those occurring in the context of clonal hematopoiesis (11).”
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“[101, 102] on human peripheral-blood cells proposed a link between clonal hematopoiesis of indeterminate potential (CHIP) with early-onset of atherosclerosis.”
BackgroundNew genetic loci associated with the risk of clonal hematopoiesis
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Dnmt3a -Mutant Hematopoietic Stem Cell Rewire IFNγ Signaling to Gain Clonal Advantage
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Clonal haematopoiesis mutations in cardiogenic shock: a beginning of a new era?
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Metadata
- Authors
- Jaiswal, S., & Ebert, B. L.
- Affiliations
- Stanford Medicine (US)
- Broad Institute (US)
- Corresponding author
- Jaiswal, Siddhartha
- Ebert, Benjamin L.
- Venue
- Science
- Published
- 2019-11
- Volume
- 366
- Issue
- 6465
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8050831
- OpenAlex
- W2982291252
- Semantic Scholar
- 6d1a7a80dacac969118008d44a082733bff68245
- Cited by
- 1,156
- References
- 98
- Citations by year
- 2026: 173 · 2025: 222 · 2024: 206 · 2023: 169 · 2022: 164 · 2021: 136 · 2020: 83 · 2019: 3
- FWCI
- 15.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Japanese Society of Hematology
- Funders
- National Institutes of Health (P01CA066996, P50CA206963, R01HL082945)
- Burroughs Wellcome Fund
- Edward P. Evans Foundation
- Ludwig Institute for Cancer Research
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- clonal hematopoiesis, somatic mutations, aging, hematopoietic stem cells, cancer risk, immune function
- MeSH terms
- Aged, Aging, Animals, Cardiovascular Diseases, Clone Cells, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mutation, Precancerous Conditions, Hematologic Neoplasms, Clonal Evolution
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