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 401–500 of 1,000
MicroRNAs in hematopoietic stem cell aging
Luinenburg, D., & de Haan, G. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111281 · Cited by 13
E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells
Ramanathan, G., Hoover, B., Arechavala, R. J., Herman, D. A., Chen, J. H., Lai, H. Y., Renusch, S. R., Kleinman, M. T., & Fleischman, A. G. (2020) · Cancers · doi:10.3390/cancers12082292 · Cited by 18
“Smoking status is also correlated with the risk of clonal hematopoiesis of indeterminate potential (CHIP) [18,19], where individuals carry a leukemia-related mutation in candidate genes at 2% variant allele frequency but without overt disease [20].”
BackgroundRudolph, K. L. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111394 · Cited by 15
Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status
Castillo, D., Yuan, T., Nehoray, B., Cervantes, A. E., Tsang, K. K., Yang, K., Sand, S. R., Mokhnatkin, J. V., Herzog, J., Slavin, T. P., et al. (2022) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-21-1296 · Cited by 15
Self-citationSherwood, K., Ward, J. C., Soriano, I., Martin, L. M., Campbell, A., Rahbari, R., Kafetzopoulos, I., Sproul, D., Green, A., Sampson, J. R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39248-0 · Cited by 18
Yun, J. K., Kim, S., An, H., Lee, G. D., Kim, H. R., Kim, Y., Kim, D. K., Park, S.-I., Choi, S., & Koh, Y. (2023) · Genome Medicine · doi:10.1186/s13073-023-01266-4 · Cited by 15
“Clonal hematopoiesis (CH) is a condition defined by the expansion of clonally derived hematopoietic stem cells (HSCs) that harbor somatic mutations in leuke-mia-associated genes, which can be detected by next-generation sequencing (NGS) [1–3].”
BackgroundLiu, C., Cheng, C., Lian, T., Zhou, Y.-P., Yang, Y., Zhang, S.-J., Zhang, S.-J., Zhu, Y.-J., Qiu, L.-H., Qiu, B., et al. (2024) · Hypertension · doi:10.1161/hypertensionaha.123.22274 · Cited by 14
Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative
Anthony, K. M., Collins, J. M., Love, S.-A. M., Stewart, J. D., Buchheit, S. F., Gondalia, R., Schwartz, G. G., Huang, D. Y. C., Meliker, J. R., Zhang, Z., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000208055 · Cited by 15
Self-citationInherent genome instability underlies trisomy 21-associated myeloid malignancies
Chen, C.-C., Silberman, R. E., Ma, D., Perry, J. A., Khalid, D., Pikman, Y., Amon, A., Hemann, M. T., & Rowe, R. G. (2024) · Leukemia · doi:10.1038/s41375-024-02151-8 · Cited by 14
Beyond BCR::ABL1—The Role of Genomic Analyses in the Management of CML
Branford, S., Fernandes, A., Shahrin, N. H., Maqsood, M., Shanmuganathan, N., & Wadham, C. (2024) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2023.7335 · Cited by 15
Cell of origin epigenetic priming determines susceptibility to Tet2 mutation
Schiroli, G., Kartha, V. K., Duarte, F. M., Kristiansen, T. A., Mayerhofer, C., Shrestha, R., Earl, A., Hu, Y., Tay, T., Rhee, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48508-6 · Cited by 15
“overall clinical adverse outcome 5,10 – 13 , representing a precursor state for myelodysplastic syndromes (MDS) and ultimately acute myeloid leukemia (AML) 14 – 16 .”
Dou, X., Dan, C., Zhang, D., Zhou, H., He, R., Zhou, G., Zhu, Y., Fu, N., Niu, B., Xu, S., et al. (2024) · International Journal of Cancer · doi:10.1002/ijc.35125 · Cited by 14
“27 Therefore, early detection of CHIP-associated mutations may provide recommendations for enhanced patient management.”
Ueda, M., Higgins, J. E., Jenkins, I., Randolph, T. W., Smith, T. H., Valentine, C. C., Salk, J. J., Yeung, C. C. S., Beppu, L. W., Campbell, J., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.ado5108 · Cited by 14
“The presence of CH has been observed to increase with age, occurring in 10 to 20% of individuals aged 70 or older ( 9 ).”
BackgroundKállai, A., Ungvari, A., Csabán, D., Őrfi, Z., Lehoczki, A., Harasztdombi, J., Yabluchanskiy, A., Benyó, Z., Szappanos, Á., Tarantini, S., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01654-1 · Cited by 14
“CHIP-mutant leukocytes exhibit increased self-renewal [110], infiltrate the atherosclerotic plaques [188], and demonstrate enhanced secretion of inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species [117, 189].”
Studying clonal evolution of myeloid malignancies using induced pluripotent stem cells
Doulatov, S. R., & Papapetrou, E. P. (2020) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000620 · Cited by 15
“Myeloid malignancies are the end product of agerelated molecular evolution of HSCs [10,11].”
BackgroundTelomere Attrition and Clonal Hematopoiesis of Indeterminate Potential in Cardiovascular Disease
Huang, Y., & Wang, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189867 · Cited by 15
“01% to >18% depending on the detection methods used in clinical trials [3,75].”
BackgroundMethodTherapy-Related Clonal Hematopoiesis
Yura, Y., Cochran, J. D., & Walsh, K. X. (2022) · Heart Failure Clinics · doi:10.1016/j.hfc.2022.02.010 · Cited by 14
Huang, Z., Vlasschaert, C., Robinson‐Cohen, C., Pan, Y., Sun, X., Lash, J. P., Kestenbaum, B. R., & Kelly, T. N. (2022) · Translational research · doi:10.1016/j.trsl.2022.12.009 · Cited by 14
Human haematopoietic stem cells remember inflammatory stress
Zeng, A. G. X., Nagree, M. S., Jakobsen, N. A., Shah, S., Varesi, A., Kang, J. R. W., Murison, A., Cheong, J.-G., Turkalj, S., Zhang, X., et al. (2026) · Nature · doi:10.1038/s41586-026-10522-7 · Cited by 10
“5a–f and Supplementary Table 13).”
InfluentialSocial, Behavioral, and Clinical Risk Factors Are Associated with Clonal Hematopoiesis
Young, C. D., Hubbard, A. K., Saint‐Maurice, P. F., Chan, I. C. C., Cao, Y., Tran, D., Bolton, K. L., Chanock, S. J., Matthews, C. E., Moore, S. C., et al. (2024) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-24-0620 · Cited by 13
The long-lived immune system of centenarians
Plaza‐Florido, A., Carrera‐Bastos, P., Pérez‐Prieto, I., Fiuza‐Luces, C., Radom‐Aizik, S., Cruz, B. D. P., Franceschi, C., López‐Soto, A., López-Otı́n, C., & Lucía, A. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01291-5 · Cited by 13
“Accumulating evidence links CHIP to heightened systemic inflammation 85 , probably through increased pro-inflammatory cytokine production from mutant myeloid clones and enhanced pattern-recognition receptor signalling, although causal pathways in humans remain incompletely defined 85 .”
InfluentialClonal hematopoiesis in patients with high‐grade B‐cell lymphoma is associated with inferior outcome
Amini, R., Ljungström, V., Abdulla, M., Cavelier, L. B., Pandzic, T., Hollander, P., Enblad, G., & Baliakas, P. (2020) · American Journal of Hematology · doi:10.1002/ajh.25927 · Cited by 13
Lee, S., Wong, H., Castiglione, M. A., Murphy, M. M., Kaushansky, K., & Zhan, H. (2022) · Stem Cells · doi:10.1093/stmcls/sxac005 · Cited by 12
Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection
Rajsri, K. S., Roy, N., & Chakraborty, S. (2023) · Cancers · doi:10.3390/cancers15102866 · Cited by 13
“Early preleukemic mutations confer clonal outgrowth advantages to these cells, and lead to clonal hematopoiesis of indeterminate potential (CHIP) [6–9].”
BackgroundVittorietti, M., Mazzola, S., Costantino, C., Bella, D. D. D., Fruscione, S., Bonaccorso, N., Sciortino, M., Costanza, D., Belluzzo, M., Savatteri, A., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1202733 · Cited by 13
“The clonal outgrowth of hematopoietic cells (clonal hematopoiesis) is highly prevalent in the elderly and predisposes to hematological malignancies including T-cell lymphomas (99).”
BackgroundEpigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease
Ogura, Y., & Mimura, I. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1281850 · Cited by 13
“JAK2 is involved in cellular growth signaling and SF3B1 is a splicing factor (Jaiswal and Ebert, 2019).”
BackgroundFunctional categorization of gene regulatory variants that cause Mendelian conditions
Cheng, Y.-H. H., Bohaczuk, S. C., & Stergachis, A. B. (2024) · Human Genetics · doi:10.1007/s00439-023-02639-w · Cited by 13
“…that intrinsically express that gene, with the exception of coding LOF variants within exons that are alternatively spliced only within certain tissues or somatic coding LOF variants that only exist within certain tissues (Poduri et al. 2013; Biesecker and Spinner 2013; Jaiswal and Ebert 2019).”
BackgroundShannon, M. L., Heimlich, J. B., Olson, S., Debevec, A., Copeland, Z., Kishtagari, A., Vlasschaert, C., Snider, C. A., Silver, A. J., Brown, D. J., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023011510 · Cited by 13
Zhang, H., Kafeiti, N., Masarik, K., Lee, S., Yang, X., Zheng, H., & Zhan, H. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.321008 · Cited by 14
Neuroimmune circuits in the plaque and bone marrow regulate atherosclerosis
Gerhardt, T., Huynh, P., & McAlpine, C. S. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae167 · Cited by 14
Aging and Cancer—Inextricably Linked Across the Lifespan
DeGregori, J. V., Seidl, K. J., & Montano, M. A. (2025) · Aging Cell · doi:10.1111/acel.14483 · Cited by 12
“…tissues (Marongiu and DeGregori 2022), which are associated with both malignant and nonmalignant disease risk as shown for the hematopoietic system (Jaiswal and Ebert 2019; Florez et al. 2022), still represent a relatively unexplored frontier, particularly regarding the impact of these clonal…”
Insights Into Heart-Tumor Interactions in Heart Failure
Caller, T., Moore, K. J., Lehmann, L., Wu, S. M., & Leor, J. (2025) · Circulation Research · doi:10.1161/circresaha.124.325490 · Cited by 15
Li, J., Wang, C., Liu, J., Yu, Y., Liu, Y., Peng, Q., Liu, H., & Guan, X. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06370-5 · Cited by 12
“And most somatic mutations are harmless, only a few mutations affect a gene or regulatory element,contributing to a phenotypic consequence[4].”
BackgroundGenetics of autosomal mosaic chromosomal alteration (mCA)
Liu, X., Kamatani, Y., & Terao, C. (2021) · Journal of Human Genetics · doi:10.1038/s10038-021-00964-4 · Cited by 13
“During the pathogenic process or aging, a subset of hematopoietic stem/progenitor cells that acquired somatic mutations may gain a proliferative or survival advantage over others and expand clonally until they become over-represented in the blood cell pool [32].”
BackgroundLongitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effectsPreprint
Robertson, N., Crespo, E. L., Terradas-Terradas, M., Purcell, A. C., Livesey, B., Marsh, J. A., Murphy, L., Murphy, L., MacGillivray, L., MacGillivray, L., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1038/s41591-022-01 · Cited by 13
Cancer and aging: A call to action
Braithwaite, D., Anton, S. D., Mohile, S. G., DeGregori, J. V., Gillis, N., Zhou, D., Bloodworth, S., Pahor, M., & Licht, J. D. (2022) · Aging and Cancer · doi:10.1002/aac2.12055 · Cited by 13
Shah, U. J., Alsulimani, A., Ahmad, F., Mathkor, D. M., Alsaieedi, A., Harakeh, S., Nasiruddin, M., & Haque, S. (2022) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2022.2108994 · Cited by 14
“Lastly, aged clinical cases may have benign tumors (e.g. skin tumors) or leukocytes carrying cancer-related mutations (Genovese et al., 2014; Jaiswal & Ebert, 2019), which might elicit as false-positive diagnosis.”
BackgroundDynamics of mutations in patients with essential thrombocythemia treated with imetelstat
Leibundgut, E. O., Haubitz, M., Burington, B. E., Ottmann, O. G., Spitzer, G., Odenike, O. M., McDevitt, M. A., Röth, A., Snyder, D., & Baerlocher, G. M. (2020) · Haematologica · doi:10.3324/haematol.2020.252817 · Cited by 12
“Experiments in mouse models carrying loss-of-function mutations in DNMT3A or TET2 suggest a competitive advantage and enhanced self-renewal capacity of the mutant stem cells leading to clonal expansion.(34) Of the other non-responsive mutations in this study, mutations affecting the splicing factor SF3B1 are uncommon…”
BackgroundVascular Aging in the Invertebrate Chordate, Botryllus schlosseri
Rodriguez, D., Taketa, D. A., Madhu, R., Kassmer, S. H., Loerke, D., Valentine, M. T., & Tomaso, A. W. D. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.626827 · Cited by 13
“Aging in these tissues is thought to be due to damage and accumulation of mutations within, often followed by competition between, the corresponding stem cells, which in turn affect the differentiated progeny (Hayflick, 1998; Beerman et al., 2010; Sousounis et al., 2014; Jaiswal and Ebert, 2019; Liu et al., 2019).”
BackgroundMistry, J. J., Young, K. A., Díaz, P. A. C., Fernández-Maestre, I., Levine, R. L., & Trowbridge, J. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.28.587254 · Cited by 11
“Aging is associated with functional decline of the hematopoietic system( 1 ) and development of clonal hematopoiesis (CH)( 2 ).”
BackgroundMechanism of age-related accumulation of mtDNA mutations in human blood
Gupta, R., Durham, T., Chau, G., Kanai, M., Uddin, M. M., Lu, W., Argentieri, M. A., Karczewski, K. J., Howrigan, D. P., Natarajan, P., et al. (2026) · Nature · doi:10.1038/s41586-026-10569-6 · Cited by 23
“These findings suggest that there are individuals with undetected CH (for instance, due to unidentified driver mutations) that can be identified on the basis of elevated mtSNV burden, consistent with work showing that CH is universally present at low fraction 44,45 .”
Clonal hematopoiesis in primary immune thrombocytopenia
Wang, Y., Yu, T., Dong, Q., Liu, S., Yu, Y., Zhao, H., Ma, J., Dong, L., Wang, L., Ma, D., et al. (2022) · Blood Cancer Journal · doi:10.1038/s41408-022-00641-5 · Cited by 12
“It was first raised in a study of X-chromosome inactivation among elderly healthy women [1], and has been extensively identified in various clinical settings as the wide use of high-throughput sequencing technologies [2, 3].”
BackgroundCheng, C., Hong, W., Li, Y., Xiao, X., McKay, J., Han, Y., Byun, J., Peng, B., Albanes, D., Lam, S. C., et al. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.05.001 · Cited by 12
van de Loosdrecht, A. A., Cremers, E. M. P., Alhan, C., Duetz, C., Hout, F. E. M. I. ’., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M. P. R. M., Ossenkoppele, G. J., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02161-6 · Cited by 12
“…by the fact that SF3B1 is frequently affected in clonal hematopoiesis of indeterminate potential, a condition increasingly occurring in elderly people with mutations at diverse VAFs [34] The observation of non-responsiveness to lenalidomide in SF3B1 -mutant del(5q) MDS is of clinical importance.”
Biological basis of extensive pleiotropy between blood traits and cancer risk
Pardo-Cea, M. Á., Farré, X., Esteve, A., Palade, J., Espín, R., Mateo, F., Alsop, E. B., Alorda, M., Blay, N., Baiges, A., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01294-8 · Cited by 12
“…influencing blood trait–cancer pleiotropism might in turn be associated with the phenomenon of “clonal hematopoiesis”: i.e., clonal expansion of hematopoietic stem cells and their progeny due to acquired somatic mutations in driver genes, frequently linked to myeloid malignancies [131, 132].”
BackgroundStańkowska, W., Sarkisyan, D., Bruhn‐Olszewska, B., Duzowska, K., Bieńkowski, M., Jąkalski, M., Wójcik, M., Davies, H., Drężek-Chyła, K., Pęksa, R., et al. (2024) · Cancers · doi:10.3390/cancers16050961 · Cited by 11
Determinants of mosaic chromosomal alteration fitness
Pershad, Y., Mack, T., Poisner, H. M., Jakubek, Y. A., Stilp, A. M., Mitchell, B. D., Lewis, J. P., Boerwinkle, E., Loos, R. J. F., Chami, N., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48190-8 · Cited by 13
Self-citationIdentification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Demajo, S., Ramis-Zaldivar, J. E., Muiños, F., Grau, M. L., Andrianova, M. A., López-Bigas, N., & González-Pérez, A. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1416 · Cited by 14
“During aging, this process frequently causes clonal hematopoiesis (CH), a state in which one stem cell–derived population occupies a large fraction of the blood cells and platelets (1–6).”
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement
Short, E. L., ICCARP, Adcock, I. M., Al-Sarireh, B., Ager, A., Ajjan, R., Akbar, N., Akeroyd, M. A., Alsaleh, G., Al-Sharbatee, G., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01315-9 · Cited by 12
“For example, clonal haematopoiesis can be clinically silent [7], but it can manifest as a patient becoming systemically unwell because of an infection (the additional insult), even if it does not develop into myelodysplasia or leukaemia.”
Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy
Wang, Z., & Zhang, J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00768-6 · Cited by 14
“Importantly, CH is associated with an increased risk of haematological malignancies and cardiovascular diseases in the general population 67 .”
InfluentialLiu, Y., Xi, Z., Zhou, J., Ling, F., Zhang, Y., Xie, H., Zheng, J., Xia, B., Feng, H., & Li, Y. (2025) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-24-1342 · Cited by 12
Loss of Y chromosome at the interface between aging and Alzheimer’s disease
Guo, X. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03935-2 · Cited by 11
Greco, S. J., Ayer, S., Guiro, K., Sinha, G., DONNELLY, R. J., El-Far, M. H., Pamarthi, S. H., Sandiford, O. A., Gergues, M., Sherman, L. S., et al. (2021) · Aging · doi:10.18632/aging.203689 · Cited by 12
“Single driver mutation in the aged hematopoietic cells can lead to the emergence of non-malignant clones of indeterminate potential (CHIP) thereby increasing the risk of hematological malignancy [16].”
Shabashvili, D. E., Feng, Y., Kaur, P., Venugopal, K., & Guryanova, O. A. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.03.008 · Cited by 14
Two faces of RUNX3 in myeloid transformation
Yokomizo‐Nakano, T., & Sashida, G. (2021) · Experimental Hematology · doi:10.1016/j.exphem.2021.02.005 · Cited by 12
DNA-methylation aging at single-cell level
Rudolph, K. L. (2021) · Nature Aging · doi:10.1038/s43587-021-00154-z · Cited by 12
Transforming mutations in the development of pathogenic B cell clones and autoantibodies*
Reed, J. H. (2022) · Immunological Reviews · doi:10.1111/imr.13064 · Cited by 13
A Concept of “Athero-Oncology”: Tumor-Like Smooth Muscle Cells Drive Atherosclerosis
Chatterjee, P., & Martin, K. A. (2024) · Circulation · doi:10.1161/circulationaha.124.069446 · Cited by 12
Sim, H., Park, H. J., Park, G., Kim, Y. J., Park, W., Lee, S., & Choi, M. (2024) · eLife · doi:10.7554/elife.96951 · Cited by 12
Yokomizo‐Nakano, T., Hamashima, A., Kubota, S., Bai, J., Sorin, S., Sun, Y., Kikuchi, K., Iimori, M., Morii, M., Kanai, A., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20220962 · Cited by 12
“…promoted the proliferation of HSCs, resulting in somatic mutations and CH (Heyde et al., 2021), which are considered to cause arteriosclerosis and fatal events in the heart and brain in humans, forming a positive feedback loop to drive transformation (Pietras, 2017; Jaiswal and Ebert, 2019).”
Waarts, M. R., Mowla, S., Boileau, M., Benitez, A. R. M., Sango, J., Bagish, M., Fernández-Maestre, I., Shan, Y., Eisman, S. E., Park, Y. C., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1092 · Cited by 13
On correlative and causal links of replicative epimutations
Zhou, W., & Reizel, Y. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.08.008 · Cited by 13
Senapati, J., Kantarjian, H. M., Habib, D. S., Haddad, F., Jain, N., Short, N. J., & Jabbour, E. (2025) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2025.2449582 · Cited by 11
“t-MN is being more commonly encountered in older patients with All as they now live longer with more effective anti-All regimens, along with their underlying predisposition from ARcH and BM genomic instability [47,57].”
Yang, Y., Cathelin, S., Liu, A. C. H., Subedi, A., Maher, A., Hosseini, M., Ayyathan, D. M., Vanner, R. J., & Chan, S. M. (2025) · Nature Communications · doi:10.1038/s41467-025-57614-y · Cited by 12
“CHIP carriers are at a higher risk of developing hematologic malignancies and other age-related in fl ammatory illnesses such as cardiovascular diseases, relative to non-carriers 1,3,4 .”
Karakasis, P., Theofilis, P., Lefkou, E. E., Antoniadis, A. P., Patoulias, D., Korantzopoulos, P. G., & Fragakis, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062739 · Cited by 14
“Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations in HSCs, leading to clonal expansion in the absence of overt hematologic malignancy [17,18].”
The role of deubiquitinases in cardiovascular diseases: mechanisms and therapeutic implications
Fei, X., Song, C., Cui, J., Li, Y., Lei, X., & Tang, H. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1582049 · Cited by 11
“CH is characterized by the presence of mutant hematopoietic cell clones with selective proliferative advantages in peripheral blood (56).”
Bahmani, F., Shayanmanesh, M., Safari, M., Alaei, A., Pouriafar, Y., Rasti, Z., Zaker, F., Rostami, S., Damerchiloo, F., & Safa, M. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03793-z · Cited by 12
“In elderly populations, these age-related changes lead to increased susceptibility to infections, anemia, autoimmunity, poor vaccine responses, and a heightened risk of hematologic malignancies [25, 35].”
Clonal Hematopoiesis and Solid Cancers
Nguyen, Y. T. M., Fujisawa, M., Ishikawa, S., & Sakata‐Yanagimoto, M. (2025) · Cancer Science · doi:10.1111/cas.70097 · Cited by 12
“DNMT3A , TET2 , and ASXL1 mutations are more common in younger individuals, while SRSF2 and SF3B1 mutations typically appear in those over 70 [2, 8, 49].”
InfluentialKirmani, 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. (2025) · Nature Communications · doi:10.1038/s41467-025-59333-w · Cited by 11
Modelling the ageing dependence of cancer evolutionary trajectories
Henry, C. J., & DeGregori, J. V. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00838-3 · Cited by 14
“…by contexts that change tissue landscapes, including sun exposure for the skin 50 , alcohol and cigarette smoking for the oesophagus 51,52 , obesity, smoking and chemotherapy in clonal haematopoiesis 53,54 , air pollution and smoking in the lung 34,55 , and ulcerative colitis in the colon 56–58 .”
Sant’Antonio, E., Camerini, C., Rizzo, V., Musolino, C., & Allegra, A. (2021) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2021.04.014 · Cited by 11
Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics
Nann, D., & Fend, F. (2021) · Cancers · doi:10.3390/cancers13143528 · Cited by 12
“5 to 1% per year, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), depending on the clone size, number of mutations and affected genes [26,27].”
BackgroundEnriched clonal hematopoiesis in seniors with dietary vitamin C inadequacy
Chen, J., Nie, D., Wang, X., Wang, L., Wang, F., Zhang, Y., Xue, C., Cao, P., Li, M., Ma, X., et al. (2021) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2021.10.014 · Cited by 11
Molecular Diagnostic Testing for Hematopoietic Neoplasms
Hergott, C. A., & Kim, A. S. (2022) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2022.04.005 · Cited by 11
Tague, L. K., Oetjen, K. A., Mahadev, A., Walter, M. J., Anthony, H., Kreisel, D., Link, D. C., & Gelman, A. E. (2023) · JCI Insight · doi:10.1172/jci.insight.165609 · Cited by 11
“Discussion CH has come to be understood as a consequence of aging and exposures such as tobacco, with the consequence of increased all-cause mortality even among individuals who never develop hematologic malignancy (2).”
InfluentialWGS and WTS in leukaemia: A tool for diagnostics?
Meggendorfer, M., Walter, W., & Haferlach, T. (2020) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2020.101190 · Cited by 11
FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia
Govindarajah, V., Lee, J.-M., Solomon, M. P., Goddard, B., Nayak, R. C., Nattamai, K., Geiger, H., Salomonis, N., Cancelas, J. A., & Reynaud, D. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020001826 · Cited by 11
“Restriction of the clonal hematopoietic diversity, a phenomenon known as clonal hematopoiesis of indeterminate potential (CHIP), is a frequent feature of aging that may precede the emergence of hematologic malignancies.(44,45) CHIP is associated with an increase in the likelihood of having type II diabetes, but the ca…”
BackgroundGrenier‐Pleau, I., & Abraham, S. A. (2021) · Experimental Hematology · doi:10.1016/j.exphem.2021.08.004 · Cited by 10
Salybekov, A. A., Wolfien, M., Kobayashi, S., Steinhoff, G., & Asahara, T. (2021) · Cells · doi:10.3390/cells10123266 · Cited by 10
“The CD133+ cells have applications in advanced treatment for patients with terminal-stage PAD[9,11].”
BackgroundAging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions
Miyawaki, M., Hashimoto, S., Ogawa, S., & Kase, Y. (2026) · Aging Cell · doi:10.1111/acel.70385 · Cited by 10
“Age-associated somatic mutations such as TET2 , DNMT3A , and ASXL1 promote the expansion of mutant hematopoietic clones, driving systemic inflammation and vascular dysfunction (Jaiswal et al. 2017; Jaiswal and Ebert 2019; Cook et al. 2020; Jaiswal and Libby 2020) (Figure 2).”
Charting single-cell lineages with synthetic and natural barcodes
Rodriguez-Fraticelli, A., & Parreno, V. (2026) · Nature Reviews Genetics · doi:10.1038/s41576-026-00943-5 · Cited by 11
“In blood ageing, this process is called clonal haematopoiesis and is driven by the expansion of HSCs and progenitor cells in the bone marrow 223 .”
A 2026 update on myelodysplastic neoplasms: current state, challenges and future directions
Bewersdorf, J. P., Mina, A. A., Stahl, M. F., & Zeidan, A. M. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01141-2 · Cited by 13
“Clonal haematopoiesis is uncommon in younger individuals, although its prevalence increases markedly with age, affecting >10% of individuals >70 years of age 99,100 .”
Jing, C., Prutsch, N., He, S., Zimmerman, M. W., Landesman, Y., & Look, A. T. (2023) · British Journal of Haematology · doi:10.1111/bjh.18667 · Cited by 11
Cacic, A. M., Schulz, F. I., Germing, U., Dietrich, S., & Gattermann, N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1303785 · Cited by 12
“The most sensitive technique, i.e. ‘ error corrected sequencing ’ (ECS) can identify point mutations and small indels from adult blood and marrow samples at a VAF as low as 0.01% (26, 174).”
BackgroundMethodInfluentialHasan, T., Pasala, A. R., Hassan, D., Hanotaux, J., Allan, D., & Maganti, H. B. (2024) · Current Oncology · doi:10.3390/curroncol31020044 · Cited by 9
“Thus, the overrepresentation of mature blood cells from the same HSC clone leads to clonal hematopoiesis (CH) [42].”
BackgroundMetabolic reprogramming regulated by TRAF6 contributes to the leukemia progression
Matsui, S., Ri, C., Bolanos, L. C., Choi, K., Shibamiya, A., Ishii, A., Takaishi, K., Oshima‐Hasegawa, N., Tsukamoto, S., Takeda, Y., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02245-3 · Cited by 10
“Notably, the presence of some driver mutations associated with AML in healthy, particularly older, individuals is indicative of a pre-leukemic state known as clonal hematopoiesis of indeterminate potential (CHIP), which increases the risk of developing myeloid malignancies [7 – 10].”
Fasouli, E. S., & Katsantoni, E. Z. (2024) · FEBS Letters · doi:10.1002/1873-3468.14985 · Cited by 12
Novel insights and therapeutic approaches in secondary AML
Marconi, G., Rondoni, M., Zannetti, B. A., Zacheo, I., Nappi, D., Mattei, A., Rocchi, S., & Lanza, F. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1400461 · Cited by 10
Xie, Y., Kazakova, V., Weeks, L. D., Gerber, J. M., Tai, J. W., Zhang, T. Y., Lowsky, R., Wu, X., Yang, C., & Patel, S. A. (2024) · Bone Marrow Transplantation · doi:10.1038/s41409-024-02403-2 · Cited by 10
Jensen, J. L., Bobek, O. J., Chan, I. C. C., Miller, B. C., Hillman, D. W., Heller, G., Druley, T. E., Armstrong, A. J., Morris, M. J., Milowsky, M. I., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-0803 · Cited by 12
DNA methylation drives hematopoietic stem cell aging phenotypes after proliferative stress
Yanai, H., McNeely, T. L., Ayyar, S., Leone, M., Zong, L., Park, B., & Beerman, I. (2024) · GeroScience · doi:10.1007/s11357-024-01360-4 · Cited by 14
“However, such mutations could also result in a selective advantage, as observed in clonal hematopoiesis of indeterminate potential (ChIP) [42], and therefore mutation accumulation is likely not a major driver of the observed loss of potential.”
Critically ill adult patients with acute leukemia: a systematic review and meta-analysis
Chean, D., Paz, D. L., Poole, D., Fodil, S., Lengliné, É., Dupont, T., Kouatchet, A., Darmon, M., & Azoulay, É. (2025) · Annals of Intensive Care · doi:10.1186/s13613-024-01409-9 · Cited by 10
Targeting innate immune memory: a new paradigm for gout treatment
Gaal, O. I., Joosten, L. A. B., & Crișan, T. O. (2025) · Exploration of Musculoskeletal Diseases · doi:10.37349/emd.2025.1007103 · Cited by 10
Targeting the cell-cycle machinery for cancer therapy
Peng, Y., Liu, J., Inuzuka, H., Liu, J., & Wei, W. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.08.008 · Cited by 12
Kibble, M., Khan, S. A., Ammad-ud-din, M., Bollepalli, S., Palviainen, T., Kaprio, J. A., Pietiläinen, K. H., & Ollikainen, M. (2020) · Royal Society Open Science · doi:10.1098/rsos.200872 · Cited by 10
“Somatic DNA mutation does occur with age [41] and will lead to minor variation even between MZ twins.”
BackgroundPreventive Cardio-Oncology: Cardiovascular Disease Prevention in Cancer Patients and Survivors
Fabiani, I., Branch, M. E., Cardinale, D. M., Middeldorp, M. E., Sanders, P., Cohen, J. B., Cainzos‐Achirica, M., Jaiswal, S., & Brown, S.-A. N. (2021) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-020-00883-1 · Cited by 11
Self-citationWu, X. J., Deng, J., Zhang, N., Liu, X., Zheng, X. L., Yan, T., Wu, Y., & Gong, Y. (2022) · BMC Cancer · doi:10.1186/s12885-022-09347-0 · Cited by 10
“All 100 patients with TET2 mutations in our study had significant alterations in blood count to exclude the possibility of CHIP.”
BackgroundClinical application of liquid biopsy in cancer patients
Chang, C., Lin, K.-C., Hsiao, N.-E., Hong, W.-A., Lin, C., Liu, T., Chang, Y., & Chang, J. (2022) · BMC Cancer · doi:10.1186/s12885-022-09525-0 · Cited by 10
“4 million protein coding mutations in HSC pool by age 70, and these mutations may cause clonal expansions [39].”
BackgroundSomatic compensation of inherited bone marrow failure
Lundgren, S., Keränen, M. A. I., Wartiovaara‐Kautto, U., & Myllymäki, M. (2022) · Seminars in Hematology · doi:10.1053/j.seminhematol.2022.07.002 · Cited by 10
Cell cycle arrest: A breakthrough in the supportive care of older cancer patients
Falandry, C., List, A. F., & Balducci, L. (2023) · Journal of the American Geriatrics Society · doi:10.1111/jgs.18350 · Cited by 10
“45–47 It is estimated that a 70 year old adult may host an average of 70 mutations per gene in their HSCs.(47) Most of these mutations are clinically irrelevant, but some may compromise function and survival of the stem cells.”
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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