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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
80 Not checked yet · 26 Own interpretation · 20 No basis given · 5 Own result
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
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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
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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
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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
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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
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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
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In the paper
“The size of these mutant clones was massive; in one study, a median of ~18% of blood cells carried the mutations 28.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
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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- It may state two separate claims as one. 31
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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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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
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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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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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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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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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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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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
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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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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.
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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
“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.
- 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
“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.
- 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
“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.
- 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
“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 201–300 of 1,000
Detection of cryptogenic malignancies from metagenomic whole genome sequencing of body fluids
Gu, W., Talevich, E., Hsu, E. D., Qi, Z., Urisman, A., Federman, S., Gopez, A., Arevalo, S., Gottschall, M., Liao, L., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00912-z · Cited by 35
Martin, E. C. S., Ferrer, A., Mangaonkar, A. A., Khan, S. P., Kohorst, M. A., Joshi, A. Y., Hogan, W. J., Olteanu, H., Moyer, A. M., Al‐Kali, A., et al. (2021) · American Journal of Hematology · doi:10.1002/ajh.26321 · Cited by 40
Haas, B. J., Dobin, A., Ghandi, M., Arsdale, A. V., Tickle, T. L., Robinson, J., Gillani, R., Kasif, S., & Regev, A. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100467 · Cited by 45
Saygin, C., Zhang, P., Stauber, J., Aldoss, I. T., Sperling, A. S., Weeks, L. D., Luskin, M. R., Knepper, T. C., Wanjari, P., Wang, P., et al. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0106 · Cited by 37
Self-citationThe effects of loss of Y chromosome on male health
Bruhn‐Olszewska, B., Markljung, E., Rychlicka-Buniowska, E., Sarkisyan, D., Filipowicz, N. H., & Dumanski, J. P. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-024-00805-y · Cited by 37
Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells
Cai, Z., Aguilera, F., Ramdas, B., Daulatabad, S. V., Srivastava, R., Kotzin, J. J., Carroll, M. P., Wertheim, G. B. W., Williams, A., Janga, S. C., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107816 · Cited by 37
“Indeed, using murine models, recent studies suggest that mutations in Tet2 define a preleukemic condition in HSCs and may induce clonal hematopoiesis of indeterminate potential (CHIP), which is a strong risk factor for blood cancer (Jaiswal and Ebert, 2019).”
MethodDecoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations
Dai, X., & Guo, X. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101342 · Cited by 39
Simeoni, F., Romero-Camarero, I., Camera, F., Amaral, F. M. R., Sinclair, O. J., Papachristou, E. K., Spencer, G. J., Lie‐A‐Ling, M., Lacaud, G., Wiseman, D. H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109725 · Cited by 36
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“It is essential for the homeostasis of hematopoietic stem/progenitor cells (HSPCs) and in the hematopoietic hierarchy and loss-of-function mutations of TET2 are prominent drivers of age-related clonal hematopoiesis (CH) in humans [2].”
BackgroundClinical implementation and current advancement of blood liquid biopsy in cancer
Watanabe, K., Nakamura, Y., & Low, S. (2021) · Journal of Human Genetics · doi:10.1038/s10038-021-00939-5 · Cited by 37
Mutation analysis links angioimmunoblastic T-cell lymphoma to clonal hematopoiesis and smoking
Cheng, S., Zhang, W., Inghirami, G., & Tam, W. (2021) · eLife · doi:10.7554/elife.66395 · Cited by 36
Alterations of Chromatin Regulators in the Pathogenesis of Urinary Bladder Urothelial Carcinoma
Hoffmann, M. J., & Schulz, W. A. (2021) · Cancers · doi:10.3390/cancers13236040 · Cited by 40
The origins and functional effects of postzygotic mutations throughout the human life span
Rockweiler, N. B., Ramu, A., Nagirnaja, L., Wong, W., Noordam, M. J., Drubin, C. W., Huang, N., Miller, B., Todres, E. Z., Vigh‐Conrad, K. A., et al. (2023) · Science · doi:10.1126/science.abn7113 · Cited by 39
Decoding Aging Hallmarks at the Single-Cell Level
Ma, S., Chi, X., Cai, Y., Ji, Z., Wang, S., Ren, J., & Liu, G. (2023) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-020722-120642 · Cited by 37
Pathogenic Mechanisms in Acute Myeloid Leukemia
Chakraborty, S., & Park, C. Y. (2022) · Current Treatment Options in Oncology · doi:10.1007/s11864-022-01021-8 · Cited by 36
Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia
Naji, N. S., Sathish, M., & Karantanos, T. (2024) · Cancers · doi:10.3390/cancers16233974 · Cited by 38
“Its prevalence rises significantly with age, and it usually results from mutations in specific genes or from gains and/or losses of larger chromosomal regions [16].”
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Clonal hematopoiesis and cardiovascular disease: deciphering interconnections
Stein, A., Metzeler, K. H., Kubasch, A. S., Rommel, K., Desch, S., Buttner, P. G., Rosołowski, M., Cross, M. A., Platzbecker, U., & Thiele, H. (2022) · Basic Research in Cardiology · doi:10.1007/s00395-022-00969-w · Cited by 40
“Since the reported prevalence of CHIP is strongly dependent on the sensitivity of the sequencing assay employed [53, 90], it is important to define the basic conditions for potential screening approaches.”
BackgroundIL-1β+ macrophages and the control of pathogenic inflammation in cancer
Caronni, N., Terza, F. L., Frosio, L., & Ostuni, R. (2025) · Trends in Immunology · doi:10.1016/j.it.2025.03.001 · Cited by 36
Cancer and myeloid clonal evolution in the short telomere syndromes
Schratz, K. E., & Armanios, M. Y. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.02.019 · Cited by 33
Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis
Miller, P. G., Sperling, A. S., Gibson, C. J., Viswanathan, K., Castellano, C. A., McConkey, M. E., Ceremsak, J. J., Taylor, M. S., Birndt, S., Perner, F., et al. (2020) · Blood · doi:10.1182/blood.2020008206 · Cited by 34
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Clonal hematopoiesis and VEXAS syndrome: survival of the fittest clones?
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Marongiu, F., & DeGregori, J. V. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13275 · Cited by 38
Mammalian DNA methylome dynamics: mechanisms, functions and new frontiers
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Gutierrez‐Rodrigues, F., Wells, K. V., Jones, A. I., Hironaka, D., Rankin, C., Gadina, M., Sikora, K. A., Alemu, L., Calado, R. T., Quinn, K. A., et al. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2023-224933 · Cited by 35
Epigenomic insights into common human disease pathology
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“Ageing-related somatic mutations in the epigenetic DNA methylome machinery, specifically DNMT3A and TET2 , are observed to be strong drivers of ageing-related clonal haematopoiesis [63].”
BackgroundHematopoiesis during Ontogenesis, Adult Life, and Aging
Belyavsky, A. V., Петинати, Н. А., & Дризе, Н. И. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179231 · Cited by 37
Cells with cancer‐associated mutations overtake our tissues as we age
Evans, E. J., & DeGregori, J. V. (2021) · Aging and Cancer · doi:10.1002/aac2.12037 · Cited by 35
The Cutting Edge of Epigenetic Clocks: In Search of Mechanisms Linking Aging and Mental Health
Harvanek, Z. M., Boks, M. P., Vinkers, C. H., & Higgins‐Chen, A. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.02.001 · Cited by 33
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“1,6,7 Accordingly, CH is associated with excess morbidity and mortality attributable to numerous chronic diseases 1,8–12 ; however, its impact on the tumor microenvironment (TME) and cancer outcomes remains unclear.”
FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome
Schieber, M., Marinaccio, C., Bolanos, L. C., Haffey, W. D., Greis, K. D., Starczynowski, D. T., & Crispino, J. D. (2020) · Blood Cancer Journal · doi:10.1038/s41408-020-00362-7 · Cited by 28
Insights into clonal hematopoiesis and its relation to cancer risk
Mitchell, S. R., Gopakumar, J., & Jaiswal, S. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.004 · Cited by 31
Self-citationAnti-CD117 immunotherapy to eliminate hematopoietic and leukemia stem cells
Russkamp, N. F., Myburgh, R., Kiefer, J. D., Neri, D., & Manz, M. G. (2021) · Experimental Hematology · doi:10.1016/j.exphem.2021.01.003 · Cited by 32
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Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium
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“The appearance and even the accumulation of mutations in HSCs and normal dividing cells are often associated with aging [11].”
BackgroundClonal Hematopoiesis: Updates and Implications at the Solid Tumor-Immune Interface
Buttigieg, M. M., & Rauh, M. J. (2023) · JCO Precision Oncology · doi:10.1200/po.23.00132 · Cited by 30
“Several studies of CH have characterized a hyperinflammatory environment, including elevated levels of tumor necrosis factor (TNF)-a, interleukin (IL)-6, and IL-1b through the activation of various inflammatory pathways.(1,17-20) The effects of DNMT3A and TET2 mutations have been best characterized in relation to infl…”
BackgroundInfluentialBone marrow niches for hematopoietic stem cells
Pereira, A. L., Galli, S., & Nombela‐Arrieta, C. (2024) · HemaSphere · doi:10.1002/hem3.133 · Cited by 35
“148 This age ‐ related clonal hematopoiesis is a manifestation of nonneutral competition in which mutations confer increased competitive fitness that manifests in a BM microenvironment shaped by aging, inflammation, or prior cytotoxic therapies.”
BackgroundReducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice
Wang, Y., Zhang, W., Zhang, C., Van, H. Q. T., Seino, T., & Zhang, Y. (2025) · Cell Research · doi:10.1038/s41422-024-01057-5 · Cited by 34
Clonal hematopoiesis of indeterminate potential and the risk of autoimmune diseases
Wu, H., Wei, J., Yu, Y., Wang, N., & Tan, X. W. (2025) · Journal of Internal Medicine · doi:10.1111/joim.20080 · Cited by 33
“As people age, tissues also accumulate somatic mutations [6, 7], occasionally granting selective growth advantages to certain cells [8].”
Fluctuating DNA methylation tracks cancer evolution at clinical scale
Gabbutt, C., Duran‐Ferrer, M., Grant, H. E., Mallo, D., Nadeu, F., Househam, J., Villamor, N., Müller, M., Heath, S. C., Raineri, E., et al. (2025) · Nature · doi:10.1038/s41586-025-09374-4 · Cited by 36
“3c), suggesting that fCpGs were detecting age-related clonal expansions of cells of the haematopoietic system 4,35,36 .”
Inflammageing and clonal haematopoiesis interplay and their impact on human disease
Hajishengallis, G., & Chavakis, T. (2026) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00936-y · Cited by 37
Periodontal Medicine Rewired: Mechanisms Linking Periodontitis to Systemic Diseases
Romandini, M., Hajishengallis, G., Curtis, M. A., & Baima, G. (2026) · Journal of Periodontal Research · doi:10.1111/jre.70099 · Cited by 36
Phosphorylation Control of p53 DNA-Binding Cooperativity Balances Tumorigenesis and Aging
Timofeev, O. N., Koch, L., Niederau, C., Tscherne, A., Schneikert, J., Klimovich, M., Elmshäuser, S., Zeitlinger, M. A., Mernberger, M., Nist, A., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2002 · Cited by 31
Jawad, M. D., Afkhami, M., Ding, Y., Zhang, X., Li, P., Young, K., Xu, M. L., Cui, W., Zhao, Y., Halene, S., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.849376 · Cited by 29
“NS Poor-very poor 13/54 (24%) 13/58 (22%) Average VAF% 27 (2-49) 28 (5-66) NS”
BackgroundHematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer
Feng, Y., Yuan, Q., Newsome, R. C., Robinson, T. M., Bowman, R. L., Zuniga, A. N., Hall, K. N., Bernsten, C. M., Shabashvili, D. E., Krajcik, K. I., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20230011 · Cited by 30
Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases
Liu, X., Xue, H., Wirdefeldt, K., Song, H., Smedby, K., Fang, F., & Liu, Q. (2024) · Journal of Internal Medicine · doi:10.1111/joim.20001 · Cited by 29
Somatic mutations in autoinflammatory and autoimmune disease
Torreggiani, S., Castellan, F. S., Aksentijevich, I. A., & Beck, D. B. (2024) · Nature Reviews Rheumatology · doi:10.1038/s41584-024-01168-8 · Cited by 30
“Some examples of autoimmune conditions in which disease course is influenced by somatic mutations include Felty syndrome in RA 79 , mixed cryoglobulinaemic vasculitis in primary Sjögren syndrome 78 , KRAS variants in systemic lupus erythematosus (SLE) 80 , and UBA1 mutations in several rheumatic…”
Implications of Clonal Hematopoiesis for Precision Oncology
Miller, P. G., & Steensma, D. P. (2020) · JCO Precision Oncology · doi:10.1200/po.20.00144 · Cited by 30
Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review
Papa, V., Marracino, L., Fortini, F., Rizzo, P., Campo, G. C., Vaccarezza, M., & Sega, F. V. D. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082480 · Cited by 29
“A growing body of evidence is pointing at clonal hematopoiesis of indeterminate potential (CHIP), defined as “the presence of clones in the absence of overt oncologic disease”, as a novel risk factor linked to the development of hematological cancers or cardiovascular diseases later in life (for a comprehensive view o…”
BackgroundAging and leukemic evolution of hematopoietic stem cells under various stress conditions
Kurosawa, S., & Iwama, A. (2020) · Inflammation and Regeneration · doi:10.1186/s41232-020-00138-3 · Cited by 29
“This phenomenon is called age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indeterminate potential (CHIP) [70, 71].”
BackgroundA DNA methylation-based liquid biopsy for triple-negative breast cancer
Cristall, K., Bidard, F., Pierga, J., Rauh, M. J., Popova, T. G., Sebbag, C., Lantz, O. J., Stern, M., & Mueller, C. R. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00198-9 · Cited by 31
Telomeres, Telomerase and Cancer
Lansdorp, P. M. (2022) · Archives of Medical Research · doi:10.1016/j.arcmed.2022.10.004 · Cited by 32
Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function
Quin, C., DeJong, E. N., Cook, E. K., Luo, M., Vlasschaert, C., Sadh, S., McNaughton, A. J. M., Buttigieg, M. M., Breznik, J. A., Kennedy, A. E., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci171002 · Cited by 29
Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia
Sirenko, M., Lee, S., Sun, Z., Chaligne, R., Loghavi, S., Asimomitis, G., Brierley, C. K., Bernard, E., Cai, S. F., Myers, R. M., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.04.012 · Cited by 28
The ageing immune system as a driver of systemic ageing
Jang, I. H., Niedernhofer, L. J., Robbins, P. D., & Camell, C. D. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01269-3 · Cited by 35
Clonal Hematopoiesis in Hospitalized Elderly Patients With COVID‐19
Hameister, E., Stolz, S. M., Fuhrer, Y., Thienemann, F., Schaer, D. J., Nemeth, J., Schuepbach, R. A., Goede, J. S., Reinhart, S., Schmidt, A. E., et al. (2020) · HemaSphere · doi:10.1097/hs9.0000000000000453 · Cited by 28
“CH is rarely found in younger individuals but its prevalence greatly and continuously increases beyond 60 years of age when it can be detected at frequencies of 10% to 20%.(4,5) Besides being a pre-malignant condition for myeloid neoplasms including acute myeloid leukemia (AML) andmyelodysplastic syndromes (MDS),(6,7)…”
BackgroundHavas, A. P., Yin, S., & Adams, P. D. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13302 · Cited by 32
Madariaga, A., Garg, S., Tchrakian, N., Dhani, N. C., Jiménez, W., Welch, S. A., MacKay, H. J., Ethier, J.-L., Gilbert, L., Li, X., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37084-w · Cited by 28
Mitigating age-related somatic mutation burden
Vijg, J., Schumacher, B., Abakir, A., Antonov, M., Bradley, C., Cagan, A., Church, G. M., Gladyshev, V. N., Gorbunova, V. A., Maslov, A. Y., et al. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.04.002 · Cited by 30
“In blood, clonally amplified mutations are most frequently detected in DNMT3A and TET2 genes involved in epigenetic regulation [89].”
Distinct landscape and clinical implications of therapy-related clonal hematopoiesis
Takahashi, K., Nakada, D., & Goodell, M. A. (2024) · Journal of Clinical Investigation · doi:10.1172/jci180069 · Cited by 32
Genetic and epigenetic alterations in aging and rejuvenation of human
Park, K., Jeon, M. C., Lee, D., Kim, J., & Im, S.-W. (2024) · Molecules and Cells · doi:10.1016/j.mocell.2024.100137 · Cited by 30
Lifelong partners: Gut microbiota-immune cell interactions from infancy to old age
Brown, J. A., Bashir, H., & Zeng, M. Y. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.01.006 · Cited by 31
Cell senescence: basic mechanisms and the need for computational networks in vascular ageing
Regnault, V., Challande, P., Pinet, F., Li, Z., & Lacolley, P. J. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa318 · Cited by 27
Devenish, L. P., Mhlanga, M. M., & Negishi, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.662565 · Cited by 27
Aged healthy mice acquire clonal hematopoiesis mutations
Chin, D. W. L., Yoshizato, T., Culleton, S. V., Grasso, F., Barbachowska, M., Ogawa, S., Jacobsen, S. E. W., & Woll, P. S. (2021) · Blood · doi:10.1182/blood.2021014235 · Cited by 27
Mechanisms of somatic transformation in inherited bone marrow failure syndromes
Choijilsuren, H. B., Park, Y., & Jung, M. (2021) · Hematology · doi:10.1182/hematology.2021000271 · Cited by 28
Whole genome deep sequencing analysis of cell-free DNA in samples with low tumour content
Ganesamoorthy, D., Robertson, A. J., Chen, W., Hall, M. B., Cao, M. D., Ferguson, K., Lakhani, S. R., Nones, K., Simpson, P. T., & Coin, L. (2022) · BMC Cancer · doi:10.1186/s12885-021-09160-1 · Cited by 28
“Clonal hematopoiesis describes the expansion of a clonal population of hematopoietic stem cells regardless of disease state [50, 51].”
Nowakowska, M. K., Kim, T., Thompson, M. T., Bolton, K. L., Deswal, A., Lin, S. H., Scheet, P. A., Wehner, M. R., & Nead, K. T. (2022) · American Journal of Hematology · doi:10.1002/ajh.26465 · Cited by 28
“the hematopoietic system that provide a competitive advantage resulting in the clonal expansion of the mutated cell population.(1) While CH was initially thought to occur primarily in the context of”
BackgroundOsteoblast Lineage Support of Hematopoiesis in Health and Disease
Kim, M., Valderrábano, R. J., & Wu, J. Y. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4678 · Cited by 29
“Clonal hematopoiesis, in which mutations in genes encoding epigenetic regulators result in clonal expansion of hematopoietic cells, becomes increasingly prevalent with age and is associated with increased risk of hematopoietic, especially myeloid, malignancies.((176)) Examination of exome sequencing data in the UK Bio…”
BackgroundEpidemiology and Pathogenesis of Myelodysplastic Syndrome
Rotter, L. K., Shimony, S. O., Ling, K., Chen, E., Shallis, R. M., Zeidan, A. M., & Stahl, M. F. (2023) · The Cancer Journal · doi:10.1097/ppo.0000000000000665 · Cited by 27
Immunological biomarkers of aging
Wu, F., Mu, W., Markov, N. T., Fuentealba, M., Halaweh, H., Senchyna, F., Manwaring-Mueller, M., Winer, D. A., & Furman, D. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkae036 · Cited by 28
“105 Altogether, these age-related changes in HSPCs appear to form the basis of immunosenescence and inflam-maging in the aging immune system.”
Convergence and divergence of individual immune responses over the life course
Metcalf, C. J. E., Graham, A. L., Yates, A. J., & Cummings, D. A. T. (2025) · Science · doi:10.1126/science.ady9543 · Cited by 26
Krishnan, V., Kim, D. D. H., Hughes, T. P., Branford, S., & Ong, S. T. (2021) · Haematologica · doi:10.3324/haematol.2021.279317 · Cited by 27
“Clonal hematopoiesis is the clinical phenomenon by which populations of hematopoietic cells expand and carry a somatic mutation that is at least 2% of the variant allele fraction.(55) The common genes comprise DNMT3A, TET2, and ASXL1, and others also found in CML individuals, including RUNX1, BCORL1, and TP53.”
BackgroundWalsh, K. X., Raghavachari, N., Kerr, C. L., Bick, A. G., Cummings, S. R., Druley, T. E., Dunbar, C. E., Genovese, G., Goodell, M. A., Jaiswal, S., et al. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.841796 · Cited by 29
“Up to 3 years of long-term follow-up revealed reproducible and significant expansion of multiple HSPC clones with heterozygous TET2 LOF mutations, compared to the limited expansion of clones carrying DNMT3A and ASXL1 mutations, reaching a VAF of as high as almost 25%.”
BackgroundInfluentialSelf-citationCumbo, C., Tarantini, F., Zagaria, A., Anelli, L., Minervini, C. F., Coccaro, N., Tota, G., Impera, L., Parciante, E., Conserva, M. R., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.873896 · Cited by 26
“On the other hand, the mutated clone itself may increase the expression of inflammatory genes in innate immune cells (8).”
BackgroundChallenges and opportunities for modeling aging and cancer
Anczuków, O., Airhart, S., Chuang, J. H., Coussens, L. M., Kuchel, G. A., Korstanje, R., Li, S., Lucido, A. L., McAllister, S. S., Politi, K. A., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.03.006 · Cited by 27
DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age
Urbanus, J. H. M., Cosgrove, J., Beltman, J. B., Elhanati, Y., Moral, R. D. A., Conrad, C., van Heijst, J. W. J., Tubeuf, E., Velds, A., Kok, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37167-8 · Cited by 25
“Importantly, this increased number of differentiation-active HSPCs could favor the occurrence of genetic mutationsassociatedwithclonalhematopoiesis 49 – 51 ,increasingtherisk of hematological malignancies associated with age.”
Andersson‐Assarsson, J. C., van Deuren, R. C., Kristensson, F. M., Steehouwer, M., Sjöholm, K., Svensson, P., Pieterse, M., Gilissen, C., Taube, M., Jacobson, P., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104621 · Cited by 27
Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes
Lee, E., An, H. Y., Lim, J., Park, K., Choi, S., Jeong, H., Kang, D., Yang, W., Kim, J., Ko, S., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26754 · Cited by 25
“3,15,26 This process might accelerate thrombogenesis in the cerebrovascular bed and induce ischemic stroke.”
BackgroundSepúlveda, H., Li, X., Arteaga-Vazquez, L. J., López-Moyado, I. F., Brunelli, M., Hernández-Espinosa, L., Yue, X., Angel, J. C., Brown, C., Dong, Z., et al. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01505-9 · Cited by 28
“…ASXL1 are the three most frequently mutated proteins in clonal hematopoeisis, a premalignant Article https://doi.org/10.1038/s41594-025-01505-9 condition that is strongly associated with aging, inflammation and cardiovascular disease 89 ; and both TET2 and ASXL1 interact robustly with OGT (refs.”
InfluentialJuvenile myelomonocytic leukemia – A bona fide RASopathy syndrome
Lasho, T. L., & Patnaik, M. M. (2020) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2020.101171 · Cited by 25
Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias
Testa, U., Castelli, G., & Pelosi, E. (2020) · Cancers · doi:10.3390/cancers12092427 · Cited by 26
Perner, F., & Armstrong, S. A. (2020) · Cells · doi:10.3390/cells9122721 · Cited by 25
“The occurrence of these mutations was found to be associated with an increased risk to develop myeloid malignancies as well as cardiovascular disease [75,79,80].”
BackgroundPetiz, L. L., Glaser, T., Scharfstein, J., Ratajczak, M. Z., & Ulrich, H. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10129-7 · Cited by 26
“Thus, this phenomenon may lead to proinflammatory profiles that correlate to an increased risk of severe diseases [5].”
BackgroundClonal hematopoiesis and cardiovascular diseases: role of JAK2V617F
Misaka, T., Kimishima, Y., Yokokawa, T., Ikeda, K., & Takeishi, Y. (2022) · Journal of Cardiology · doi:10.1016/j.jjcc.2022.02.001 · Cited by 25
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Identification of a human hematopoietic stem cell subset that retains memory of inflammatory stressPreprint
Zeng, A. G. X., Nagree, M. S., Jakobsen, N. A., Shah, S., Murison, A., Cheong, J.-G., Turkalj, S., Lim, I., Jin, L.-Q., Araújo, J., et al. (2023) · bioRxiv · doi:10.1101/2023.09.11.557271 · Cited by 15
“HSCs show functional decline with age ( 5 – 10 ), with a variable but often marked decrease in HSC clonal diversity ( 11 ), and a consequent increase in incidence of clonal hematopoiesis (CH) ( 12 ) and risk of blood malignancy ( 13 ).”
BackgroundTransposable elements as instructors of the immune system
Schmidleithner, L., Stüve, P., & Feuerer, M. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01172-3 · Cited by 35
“Owing to clonal haematopoiesis — a common ageing-related phenomenon in which blood cells derived from a single clone are over-represented 43 — clones with novel TE transpositions could be further enriched, potentially contributing to different haematological malignancies and ageing.”
Prummel, K. D., Woods, K., Kholmatov, M. M., Schmitt, E. C., Vlachou, E. P., Labyadh, M., Wehner, R., Poschmann, G., Stühler, K., Winter, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65803-y · Cited by 30
Genetics of Myelodysplastic Syndromes
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Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk
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“Relative to JAK2, ASXL1, and TET2 carriers are 3.3 and 3.9 years older, while PPM1D, SF3B1, and SRSF2 carriers are 5.0, 6.9, and 7.7 years older, respectively [4••].”
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Genetic Modifiers of Sickle Cell Disease
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Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells
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“13,16,50,51 Hence, we posited that transcriptomic and epitranscriptomic (post-transcriptional) rather than genomic alterations may prevail as drivers of LSC generation in children.”
SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation
Chen, C.-W., Zhang, L., Dutta, R. K., Niroula, A., Miller, P. G., Gibson, C. J., Bick, A. G., Reyes, J. M., Lee, Y.-T., Tovy, A., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.09.011 · Cited by 28
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“[14] Recently, CHIP has also been linked to increased susceptibility to SLD and severe liver disease.”
BackgroundPicking Winners and Losers: Cell Competition in Tissue Development and Homeostasis
Kim, W., & Jain, R. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.04.003 · Cited by 25
“Clones are infrequently detected in individuals under age 40, but the chances of detecting a clone increase in a nearly stepwise manner with age thereafter [52, 53].”
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“They are often encountered incidentally through cfDNA sequencing([55,56]).”
Background
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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