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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 501–600 of 1,000
Analysis of Somatic Mutations in Senescent Cells Using Single-Cell Whole-Genome Sequencing
Zhang, L., Cecco, M. D., Lee, M., Hao, X., Maslov, A. Y., Montagna, C., Campisi, J., Dong, X., Sedivy, J. M., & Vijg, J. (2023) · doi:10.59368/agingbio.20230005 · Cited by 10
“In cancer as well as aging of the hematopoietic system, clonal development of somatic cell lineages has often been observed and associated with health status of human subjects 22,23 .”
BackgroundMolecular and functional characteristics of megakaryocytes and platelets in aging
Esparza, O., Higa, K. C., & Davizon‐Castillo, P. (2020) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000601 · Cited by 11
Human skeletal stem cell aging
Ambrosi, T. H., Goodnough, L. H., & Chan, C. K. F. (2020) · Aging · doi:10.18632/aging.104034 · Cited by 10
Haematopoietic ageing through the lens of single-cell technologies
Strzelecka, P. M., & Damm, F. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.047340 · Cited by 10
“Recent studies implicate an altered inflammation profile of monocyte-derived macrophages as one of the factors contributing to cardiovascular disease in elderly people with clonal haematopoiesis (Jaiswal and Ebert, 2019).”
BackgroundMartin, E. C. S., Ferrer, A., Wudhikarn, K., Mangaonkar, A. A., Hogan, W. J., Tefferi, A., Gangat, N., Lasho, T. L., Altman, J. K., Godley, L. A., et al. (2021) · American Journal of Hematology · doi:10.1002/ajh.26250 · Cited by 10
Clonal Hematopoiesis: Confluence of Malignant and Nonmalignant Diseases
Lin, A. E., Rauch, P. J., Jaiswal, S., & Ebert, B. L. (2022) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-060121-120026 · Cited by 8
Self-citationNam, A. S., Dusaj, N. N., Izzo, F., Murali, R., Myers, R. M., Mouhieddine, T. H., Sotelo, J., Benbarche, S., Waarts, M. R., Gaiti, F., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.14.476225 · Cited by 10
Jakubek, Y. A., Smith, A. P., Leng, X. I., Hall, M. E., Ezzat, D., Pershad, Y., Collins, J. M., Uddin, M. M., Fardo, D. W., Natarajan, P., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70737 · Cited by 9
“Grant/AwardNumbers:75N92021D00001, 75N92021D00002,75N92021D00003, 75N92021D00004,75N92021D00005 portional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.”
Self-citationNguyen, H.-T., Luong, B. A., Tran, D. H., Nguyen, T.-H., Ngo, Q. D., Le, L. G. H., Ho, Q. C., Nguyen, H. H. T., Nguyen, C. M., Tran, V. U., et al. (2021) · Cancer Investigation · doi:10.1080/07357907.2021.2017951 · Cited by 6
“Previous studies have reported a link between individual’s ages and detection rates of CHIP-associated mutations (41,42).”
BackgroundDiagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications
Simoni, Y., & Chapuis, N. (2022) · Diagnostics · doi:10.3390/diagnostics12071659 · Cited by 9
Clonal hematopoiesis and bone marrow inflammation
Xie, X., Su, M., Ren, K., Ma, X., Lv, Z., Li, Z., Mei, Y., & Ji, P. (2022) · Translational research · doi:10.1016/j.trsl.2022.11.004 · Cited by 10
Heilmann, A. M., Riess, J. W., McLaughlin-Drubin, M. E., Huang, R. S. P., Hjulstrom, M., Creeden, J., Alexander, B. M., & Erlich, R. (2023) · The Oncologist · doi:10.1093/oncolo/oyad251 · Cited by 9
“49,50 As these alterations may be derived from hematopoietic stem cell clones instead of the profiled tumor and may have clinical implications, 51 they are being highlighted to the ordering physician for clinical correlation and potential further hematological workup and have been observed in 10%…”
BackgroundPKD1 mutant clones within cirrhotic livers inhibit steatohepatitis without promoting cancer
Zhu, M., Wang, Y., Lu, T., Guo, J., Li, L., Hsieh, M.-H., Gopal, P., Han, Y., Fujiwara, N., Wallace, D. P., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.05.015 · Cited by 9
Pellagatti, A., & Boultwood, J. (2024) · Advances in Biological Regulation · doi:10.1016/j.jbior.2024.101055 · Cited by 10
The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy
Verdonschot, J. A. J., Fuster, J. J., Walsh, K. X., & Heymans, S. R. B. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae682 · Cited by 14
Clonal hematopoiesis: elements associated with clonal expansion and diseases
Ryu, G., Koh, Y., Jaiswal, S., & Yoon, S. (2025) · Blood Research · doi:10.1007/s44313-025-00065-7 · Cited by 9
“Similarly, DNMT3A deficiency in macrophages and mast cells increases the expression of inflammatory genes [45].”
Self-citationX-linked competition — implications for human development and disease
Boone, P. M., Buenaventura, T., King, J. W. D., & Merkenschlager, M. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00840-3 · Cited by 9
Risk of Hematologic Malignancies in Patients With Acute Myocardial Infarction
Yoon, S. Y., Kim, M., Kim, H., Bang, D. W., Park, B., Jeong, S. Y., Lee, M.-Y., Kim, K. H., Lee, N.-S., Won, J.-H., et al. (2025) · JACC CardioOncology · doi:10.1016/j.jaccao.2025.04.003 · Cited by 9
Mangaonkar, A. A., Bolton, K. L., & Patnaik, M. M. (2026) · American Journal of Hematology · doi:10.1002/ajh.70205 · Cited by 13
“CH mutations such as DNMT3A , TET2 , ASXL1 , and JAK2 each have been shown to offer a distinct proliferative advantage [115, 116], but there are certain CH mutations such as the splicing factor mutations ( SF3B1 , SRSF2 , and U2AF1 ) which have a competitive disadvantage (demonstrated in in vivo…”
Suspected clonal hematopoiesis as a natural functional assay of TP53 germline variant pathogenicity
Fortuño, C., McGoldrick, K., Pesaran, T. F., Dolinsky, J. S., Hoang, L., Weitzel, J. N., Beshay, V., Leong, H. S., James, P. A., & Spurdle, A. B. (2021) · Genetics in Medicine · doi:10.1016/j.gim.2021.10.018 · Cited by 9
Yamada, Y., Muro, K., Takahashi, K., Baba, H., Komatsu, Y., Satoh, T., Goto, M., Mishima, H., Watanabe, M., Sakata, Y., et al. (2020) · Global Health & Medicine · doi:10.35772/ghm.2020.01050 · Cited by 9
“Decreased hematopoietic capacity and proliferation of monoclonal hematopoietic cells in the elderly may affect the higher incidence of leukopenia and neutropenia despite relatively mild SOX/bevacizumab effects on bone marrow suppression (32).”
BackgroundA mosaic analysis system with Cre or Tomato expression in the mouse
Wang, Q., Lin, Y., Zhang, B., Wu, J., Roy, S., Ratiu, J. J., Xu, Y., Dai, M., Hale, L. P., Xiong, Y., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014308117 · Cited by 9
MRN Complex and Cancer Risk: Old Bottles, New Wine
Elkholi, I. E., Foulkes, W. D., & Rivera, B. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1509 · Cited by 9
“Despite the fact that expanded clones are not malignant due to the lack of transformation beyond expansion, CH might predispose to hematologicmalignancies (45).”
BackgroundUtility of plasma cell-free DNA for de novo detection and quantification of clonal hematopoiesis
Gutierrez‐Rodrigues, F., Beerman, I., Groarke, E. M., Patel, B. A., Spitofsky, N., Dillon, L. W., Raffo, D. Q., Hourigan, C. S., Kajigaya, S., Ferrucci, L., et al. (2021) · Haematologica · doi:10.3324/haematol.2021.279230 · Cited by 9
“parallel sequencing have been utilized in practice as they are minimally invasive, and tumorderived cfDNA shows a good correlation with tissue genotypes.(3-5) However, more than 50% of somatic variants identified in circulating DNA derive from blood cells and are consistent with clonal hematopoiesis (CH),(4,6) a pheno…”
BackgroundMoon, I., Kong, M. G., Ji, Y. S., Kim, S. H., Park, S. K., Suh, J., & Jang, M. (2022) · Annals of Laboratory Medicine · doi:10.3343/alm.2023.43.2.145 · Cited by 9
“Inflammation plays a pivotal role in the pathogenesis of CHIP caused by mutations in DNMT3A and TET2 and CHIP-associ-ated diseases [7-9].”
Abnormal Platelet Counts and Clonal Hematopoiesis in the General Population
Kamphuis, P., van Bergen, M. G. J. M., van Zeventer, I. A., de Graaf, A. O., Dinmohamed, A. G., Salzbrunn, J. B., Schuringa, J. J., van der Reijden, B. A., Huls, G. A., & Jansen, J. H. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000821 · Cited by 10
Methylation clocks fail to generalize across genetically admixed individuals
Cruz-González, S., Okpala, O., Gu, E., Gomez, L., Mews, M., Vance, J. M., Cuccaro, M. L., Cornejo‐Olivas, M., Feliciano‐Astacio, B. E., Byrd, G. S., et al. (2025) · eLife · doi:10.1101/2024.10.16.618588 · Cited by 13
“The cell type composition in blood is known to change with age, which if not accounted for, can confound age acceleration estimates (Jaiswal and Ebert, 2019).”
Clonal hematopoiesis, aging and Alzheimer’s disease
Sánchez Vela, P., Trowbridge, J. J., & Levine, R. L. (2023) · Nature Medicine · doi:10.1038/s41591-023-02406-4 · Cited by 8
Germline predisposition for clonal hematopoiesis
Kubota, Y., & Viny, A. D. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.01.007 · Cited by 9
A tower of babel of acronyms? The shadowlands of MGUS/MBL/CHIP/TCUS
Bravo‐Pérez, C., & Gurnari, C. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.01.004 · Cited by 8
Munari, S., Ciotti, G., Cestaro, W., Corsi, L., Tonin, S., Ballarin, A., Floriani, A., Dartora, C., Bosi, A., Tacconi, M., et al. (2024) · Drugs in Context · doi:10.7573/dic.2024-3-5 · Cited by 8
“36 As already mentioned, a bone marrow study was not performed in our patient; therefore, data on the histological structure are not available.”
BackgroundClonal Hematopoiesis from a Diagnostic Perspective: 10 Years of CHIP
Kjær, L., Skov, V., Larsen, M. K., Kristiansen, M. H., Wienecke, T., Cordua, S., Ellervik, C., Langabeer, S. E., & Hasselbalch, H. C. (2024) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-024-00737-7 · Cited by 9
Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders
Zhang, Q., Yim, R., Lee, P., Chin, L., Li, V., & Gill, H. (2024) · Cancers · doi:10.3390/cancers16234118 · Cited by 10
“CH is also an independent risk factor for cardiovascular diseases (CVDs) and all-cause mortality [7,8].”
Clonal hematopoiesis of indeterminate potential: contribution to disease and promising interventions
Li, C., Zhang, C., & Li, X. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05261-8 · Cited by 8
“Growing evidence indicates that, in addition to traditional risk factors, other contributors play a role in the link between obesity and CVD [145, 146].”
Inherited resilience to clonal hematopoiesis by modifying stem cell RNA regulation
Agarwal, G., Antoszewski, M., Xie, X., Pershad, Y., Arora, U. P., Poon, C.-L., Lyu, P., Lee, A. J., Guo, C., Ye, T., et al. (2026) · Science · doi:10.1126/science.adx4174 · Cited by 10
Interplay of Skin Aging: Mitochondrial Stress and Ultraviolet Exposure
Liao, W., Wang, Y., Wang, Y., Liao, J., Chen, N., Jia, C., & Zeng, L. (2026) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/phpp.70089 · Cited by 8
“Small insertions and deletions, often resulting from replication slippage or imperfect repair of oxidative strand breaks, can cause frameshift mutations [77].”
Solimando, A. G., Melaccio, A., Vacca, A., & Ria, R. (2022) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2021.166 · Cited by 9
Mosaic Chromosomal Alterations and Human Longevity
Leshchyk, A., Xiang, Q., Andersen, S. L., Gurinovich, A., Song, Z., Lee, J. H., Christensen, K., Yashin, A. I., Wojczynski, M. K., Schwander, K., et al. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad095 · Cited by 8
Clonal Hematopoiesis: Origins and determinants of evolution
Mendez, L., & Patnaik, M. M. (2023) · Leukemia Research · doi:10.1016/j.leukres.2023.107076 · Cited by 8
Genetic Predisposition to Clonal Hematopoiesis
Quirós, P. M., & Vassiliou, G. S. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000947 · Cited by 8
Ando, Y., Munetsuna, E., Yamada, H., Ikeya, M., Teshigawara, A., Kageyama, I., Nouchi, Y., Wakasugi, T., Yamazaki, M., Mizuno, G., et al. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122315 · Cited by 8
Dnmt3a-null hematopoietic stem and progenitor cells expand after busulfan treatment
Chen, J., Matatall, K. A., Feng, X., Hormaechea‐Agulla, D., Maharjan, M., Young, N. S., & King, K. Y. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.09.192 · Cited by 8
“Mutations in the gene encoding DNA Methyltransferase 3A ( DNMT3A ) are the most common in c lonal hematopoiesis (CH), an age-related condition that was recently demonstrated to affect outcomes in patients undergoing hematopoietic stem cell transplant (HSCT).”
BackgroundInfluentialMohrin, M. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.034 · Cited by 9
Alikhan, M. A., Jaw, J., Shochet, L. R., Robson, K. J., Ooi, J. D., Brouwer, E., Heeringa, P., Holdsworth, S. R., & Kitching, A. R. (2021) · Lara D. Veeken · doi:10.1093/rheumatology/keab682 · Cited by 8
Kato, H., Maezawa, Y., Nishijima, D., Iwamoto, E., Takeda, J., Kanamori, T., Yamaga, M., Mishina, T., Takeda, Y., Izumi, S., et al. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.02.005 · Cited by 8
Defining Higher-Risk Chronic Myeloid Leukemia: Risk Scores, Genomic Landscape, and Prognostication
Shahrin, N. H., Wadham, C., & Branford, S. (2022) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-022-00668-2 · Cited by 8
Cardiovascular Mortality Risk in Patients with Bladder Cancer: A Population-Based Study
Wang, S., Ge, C., & Zhang, J. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9080255 · Cited by 8
Single Cell Transcriptomics to Understand HSC Heterogeneity and Its Evolution upon Aging
Hérault, L., Poplineau, M., Rémy, É., & Duprez, E. (2022) · Cells · doi:10.3390/cells11193125 · Cited by 9
“The partial overlap between studies could also very well be a consequence of heterogeneous aging capture, consistent with the theory of clonal hematopoiesis, which shows that competitive clones emerge and amplify at the expense of others during an individual’s lifetime [96].”
ResultClonal selection parallels between normal and cancer tissues
Salavaty, A., Azadian, E., Naik, S. H., & Currie, P. D. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.01.007 · Cited by 8
Tuke, M. A., Tyrrell, J., Ruth, K. S., Beaumont, R. N., Wood, A. R., Murray, A., Frayling, T. M., Weedon, M. N., & Wright, C. F. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.06.001 · Cited by 8
Burns, S. S., & Kapur, R. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.06.021 · Cited by 9
“15 j 292–306 j August 11, 2020 j a 2020 The A This is an open access article under the CC BY-NC-ND license (http://creativ ated sex combs-like 1 (ASXL1) genes, are commonlymutated in CHIP (Jaiswal and Ebert, 2019).”
BackgroundInfluentialCastiglione, M. A., Zhang, H., Kaushansky, K., & Zhan, H. (2021) · Experimental Hematology · doi:10.1016/j.exphem.2021.06.003 · Cited by 7
Köhrer, S., Dittrich, T., Schorb, M., Weinhold, N., Haberbosch, I., Börmel, M., Pajor, G., Goldschmidt, H., Müller‐Tidow, C., Raab, M. S., et al. (2023) · Leukemia · doi:10.1038/s41375-023-02056-y · Cited by 9
“Clonal hematopoiesis of indeterminate potential (CHIP), de fi ned by a clonal population of blood cells bearing a point mutation in a gene that is recurrently mutated in hematologic malignancies, has been associated with risk of myeloid malignancies [29, 31, 32, 44, 45].”
BackgroundDhuri, K., & Alachkar, H. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104271 · Cited by 7
Yao, S., Guo, R., Tian, W., Zheng, Y., Hu, J. J., Han, G., Yin, R., Zhou, F., & Zhang, H. (2024) · Blood Science · doi:10.1097/bs9.0000000000000206 · Cited by 7
In vivo selection of hepatocytes
Vonada, A., & Grompe, M. (2024) · Hepatology · doi:10.1097/hep.0000000000001143 · Cited by 8
Wong, R. S. M., Jang, J. H., Wong, L. L. L., Kim, J. S., Rojnuckarin, P., Goh, Y. T., Ueda, Y., Chou, W., Lee, J. W., Kanakura, Y., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212160 · Cited by 7
Zuo, C., Fu, D., Huang, Y., Li, J., Yang, S., Cheng, X., Zhang, G., Ma, T., Peng, Q., & Tan, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-02639-8 · Cited by 8
Al‐Qazazi, R., Emon, I. M., Potus, F., Martin, A. Y., Lima, P., Vlasschaert, C., Ott, B. P., Chen, K., Wu, D., Dasgupta, A., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf611 · Cited by 7
“16 CHIP variants, including TET2 and DNMT3A , increase the risk of myeloid neoplasms, like myelodysplastic syndromes and acute myeloid leukaemia, 17–19 and cardiovascular diseases, including atherosclerotic coronary artery disease.”
The Interplay of Aging and Cancer: Mechanisms, Implications, and Therapeutic Strategies
Wang, L., Luo, Y., Chen, X., Wang, Y., & Zhang, Y. (2025) · MedComm – Oncology · doi:10.1002/mog2.70041 · Cited by 8
Space-associated stem cell hallmarks of aging and resilience in astronauts
Pham, J., Nandi, S. P., Balaian, L., Engstrom, C., Chang, P. C., Mack, K., van der Werf, I. M., Klacking, E. E., Sneifer, J. S., Katragadda, N., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.11.001 · Cited by 7
Lettera, E., Ricci, L. B., Carsana, E., Giannetti, K., Tavella, T., Seffin, L., Farina, G., Gualandi, N., Quaranta, P., Furno, E. L., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20251805 · Cited by 11
“…age, and the increased incidence of myelo-proliferative disorders and hematopoietic myeloid malignancies in aged individuals (Henry et al., 2010; Jaiswal and Ebert, 2019; Signer et al., 2007; Vas et al., 2012; von Bonin et al., 2021) in mice, human HSPC aging is associated with a prominent…”
Lee, W. J., Jung, K., Song, H., Lee, H., Park, H. E., Koh, Y., Choi, S., & Park, K. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14114 · Cited by 6
RNA splicing factor Rbm25 underlies heterogeneous preleukemic clonal expansion in mice
Bramlett, C. S., Eerdeng, J., Du, J., Lee, Y., Garcia, I., Vergel-Rodriguez, M., Condie, P., Nogalska, A., & Lu, R. (2023) · Blood · doi:10.1182/blood.2023019620 · Cited by 8
La, J., Lee, M. H., Brophy, M. T., Do, N., Driver, J. A., Tuck, D. P., Fillmore, N. R., & DuMontier, C. (2023) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2023.2254434 · Cited by 7
“On the other hand, the proposed biologic mechanisms underlying frailty – e.g. increased risk of genomic instability [44], mitochondrial dysfunction [45], and inflammation [46,47] – could also underlie the development of AML.”
BackgroundZinc and aging: a narrative review of the effects on hematopoiesis and its link with diseases
Lima, F. D. S., Gonçalves, C. E. D. S., & Fock, R. A. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad115 · Cited by 11
Metabolic regulation of aged hematopoietic stem cells: key players and mechanisms
Karimnia, N., Harris, J., Heazlewood, S. Y., Cao, B., & Nilsson, S. K. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.09.006 · Cited by 7
Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders
Lasho, T. L., & Patnaik, M. M. (2023) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-023-00719-2 · Cited by 8
“TBDs also have been associated with an elevated risk of developing CH which has the capacity to clonally expand the blood compartment [23 •• , 25, 26, 32 •• ].”
InfluentialMendoza, M. F., Suan, N. M., & Lavie, C. J. (2024) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk9030131 · Cited by 11
Todorovski, A., Wang, T., Carrier, M., & Xu, Y. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024014430 · Cited by 7
Inotuzumab Ozogamicin as First-Line Therapy in Acute Lymphoblastic Leukemia
Jabbour, E. J., Rousselot, P. H., Gökbuget, N., Chevallier, P., Kantarjian, H. M., & Stelljes, M. (2025) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2024.12.016 · Cited by 7
Zimmermann, M. T., Mathison, A., Stodola, T. J., Evans, D. B., Abrudan, J., Demos, W., Tschannen, M., Aldakkak, M., Geurts, J. L., Lomberk, G. A., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.606820 · Cited by 7
“somatic databases Yes G and S 11 (9) Pre”
BackgroundStem cell concepts in myelodysplastic syndromes: lessons and challenges
Woll, P. S., & Jacobsen, S. E. W. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13283 · Cited by 7
Epperly, M. W., Shields, D. S., Fisher, R., Hou, W., Wang, H., Hamade, D. F., Mukherjee, A., & Greenberger, J. S. (2021) · Radiation Research · doi:10.1667/rade-20-00286.1 · Cited by 8
Advances in colorectal cancer genomics and transcriptomics drive early detection and prevention
Lam, K. K., Thean, L. F., & Cheah, P. Y. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106032 · Cited by 7
Oh, T. J., Song, H., Koh, Y., & Choi, S. H. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1337 · Cited by 7
“Clonal hematopoiesis of indeterminate potential (CHIP) is defined as an expansion of hematopoietic stem cells (HSCs) driven by somatic mutations without the development of any hematologic malignancy [1].”
BackgroundClonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome
Díez-Díez, M., Amorós-Pérez, M., de la Barrera, J., Vázquez, E., Quintas, A., Pascual-Figal, D. A., Dopazo, A., Sánchez‐Cabo, F., Kleinman, M. E., Gordon, L. B., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00607-2 · Cited by 8
Russell, B. E., Kianmahd, R. R., Munster, C., Yu, A., Ahad, L., & Tan, W. (2023) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63125 · Cited by 7
“Individuals also commonly acquire age-related loss-of-function ASXL1 variants due to clonal hematopoiesis (Jaiswal & Ebert, 2019).”
BackgroundThe impact of epigenetic modifications on allogeneic hematopoietic stem cell transplantation
Ktena, Y. P., Dionysiou, M., Gondek, L. P., & Cooke, K. R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1188853 · Cited by 7
“CHIP has been recently identified as a new precursor state for myeloid malignancies (26, 27).”
BackgroundGermline predisposition to clonal hematopoiesis
Liu, J., Osman, A. E. G., Bolton, K. L., & Godley, L. A. (2023) · Leukemia Research · doi:10.1016/j.leukres.2023.107344 · Cited by 7
Clonal haematopoiesis and COVID‐19: A possible deadly liaison
Shivarov, V. S., & Ivanova, M. (2020) · International Journal of Immunogenetics · doi:10.1111/iji.12503 · Cited by 7
“…explanations for this age-related skewness of the immune response but in the last several years it becomes more and more evident that at least part of this process is associated with the clonal proliferation of blood cells without overt malignancy (Cook, Luo, & Rauh, 2020; Jaiswal & Ebert, 2019).”
BackgroundAmbrosi, T. H., & Chan, C. K. F. (2021) · Current topics in microbiology and immunology · doi:10.1007/978-3-030-86016-5_1 · Cited by 7
“Inversely, the development of features such as increased expansion, myeloid skewing, and CHIP in HSPCs could also be caused by selective pressure from an altered microenvironmental signaling.”
BackgroundAdult Low-Hypodiploid Acute Lymphoblastic Leukemia Evolves from TP53 -Mutated Clonal Hematopoiesis
Saiki, R., & Ogawa, S. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0006 · Cited by 7
Histiocytes set on the heart: cardiac complications of Erdheim–Chester disease
Collin, M. P. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehac769 · Cited by 7
“ECD is a form of clonal haematopoiesis but not simply an age-related clonal haematopoiesis of indeterminate potential—also known as ‘CHIP’.8 ECD has very definite disease-causing potential in the cardiovascular system, depositing neoplastic activated macrophags in multiple locations—a kind of ‘super-CHIP’.”
BackgroundClonal Hematopoiesis in Patients With Cancer: How Much Should We Care?
Renneville, A., Bernard, E., & Micol, J. (2023) · JCO Precision Oncology · doi:10.1200/po.23.00417 · Cited by 7
Decoding functional hematopoietic progenitor cells in the adult human lungPreprint
Conrad, C., Magnen, M., Tsui, J. L., Wismer, H., Naser, M., Venkataramani, U., Samad, B., Cleary, S. J., Qiu, L., Tian, J. J., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3576483/v2 · Cited by 7
“4 HSCs are central to the pathogenesis of serious disorders including myelodysplasia, acute and chronic leukemia, aplastic anemia 5 and clonal hematopoiesis 6 , and HSC transplantation can be a life-saving therapy.”
Tet2 deficiency–induced expansion of monocyte-derived macrophages promotes liver fibrosis
Feng, J., Wu, B., Li, Y., Sun, P., Liu, Q., Xiao, Q., Cai, J.-B., Zheng, Y., Chen, H., Xu, Y., et al. (2026) · Journal of Experimental Medicine · doi:10.1084/jem.20251114 · Cited by 6
“Notably, TET2 mutations in myeloid cells are detected in ∼ 10% of individuals over 65 years old, making CHIP significantly more prevalent in the elderly (Ferrone et al., 2020; Jaiswal and Ebert, 2019; Genovese et al., 2014).”
Gelli, E., Martinuzzi, C., Soncini, D., Conticello, C., Ladisa, F., Giorgetti, G., Truffelli, D., Traverso, I., Lai, F., Guolo, F., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-79748-7 · Cited by 6
“Recent studies have identified the presence of somatic mutations in hematopoietic cells in the blood of aging individuals, a condition referred as clonal hematopoiesis of unknown significance (CHIP) 36 .”
A complex systems approach to mosaic loss of the Y chromosome
Guo, X., & Dai, X. (2024) · GeroScience · doi:10.1007/s11357-024-01468-7 · Cited by 6
“Large cohort studies have demonstrated that CH, either derived by pathogenic SNVs or CAs, is age-dependent in healthy individuals [2].”
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“This accumulation of somatic mutations during human aging leading to clonal blood cell expansion is known as clonal haematopoiesis [2].”
Marshall, C. H., Arafa, A. T., Jaeger, E., Fragkogianni, S., Sonnenschein, A., Mauer, E. A., Gondek, L. P., Chao, C. Y., Luo, J., & Antonarakis, E. S. (2025) · Cancers · doi:10.3390/cancers17091432 · Cited by 6
“This cut point was chosen as the clinical consequences of CH at variant allele frequencies of this level are the most commonly studied [4].”
Role of stem cells in ageing and age-related diseases
Chaudhary, J. K., Danga, A. K., Kumari, A., Bhardwaj, A., & Rath, P. C. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112069 · Cited by 6
Clonal Hematopoiesis: Impact on Health and Disease
Caiado, F., & Manz, M. G. (2025) · Hematological Oncology · doi:10.1002/hon.70075 · Cited by 7
“This is attributed to both, a loss and suppression of blood production from HSCs due to age‐associated dysfunctions [3] and to the continuous selection and expansion of HSC clones carrying driver‐mutations, rendering them fitter relatively to their non‐ mutant counterparts [4].”
Patterns and drivers of 43,617 mosaic chromosomal alterations in blood
Tang, D. S.-H., Kamitaki, N., Mukamel, R. E., Rubinacci, S., & Loh, P. (2026) · Nature Genetics · doi:10.1038/s41588-026-02592-0 · Cited by 7
Impact of clonal hematopoiesis on cardiovascular outcomes in cancer patients of the UK Biobank
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Manso, B. A., Medina, P., Smith‐Berdan, S., y Baena, A. R., Bachinsky, E., Mok, L., Deguzman, A., Avila, S. B., Voorhis, C. V., Chattopadhyaya, S., et al. (2025) · Aging Cell · doi:10.1111/acel.70221 · Cited by 6
Bhowmik, S., Bose, A., & Sengupta, A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1660709 · Cited by 8
5mC and 5hmC methylation sequencing: the power of 6-base sequencing in a multiomic era
Crawford, R., Charlesworth, T., Riffle, S., Yardley, K., & Osborne, R. J. (2025) · Epigenomics · doi:10.1080/17501911.2025.2586452 · Cited by 7
“Although initially viewed as benign, recent findings indicate that CH is associated with an increased risk of hematologic cancer and cardiovascular disease, as well as overall mortality for these conditions [124].”
Hanemaaijer, E. S., Müskens, K. F., Kal, I. J., Chen, L., Pas, B. M. T., Fryzik, P., Epskamp, N., van der Meulen, M., Balwierz, A., Jayalatha, A. K. S., et al. (2026) · Nature Immunology · doi:10.1038/s41590-026-02422-9 · Cited by 8
Pathophysiological roles of monocytes and macrophages in cancer
Ji, L., Li, J., Hsu, T.-W., & Li, M. O. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01296-0 · Cited by 8
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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