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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 301–400 of 1,000
Aging and comprehensive molecular profiling in acute myeloid leukemia
Li, J., Cheng, W., Lin, X., Wen, L., Wang, K., Zhu, Y., Zhu, H., Chen, X., Zhang, Y., Yin, W., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319366121 · Cited by 30
“CH is not only closely associated with malignant blood diseases such as myelodysplastic syndromes (MDS), mye-loproliferative neoplasms, and AML (14) but also shows the risk of development toward other systemic diseases (15).”
BackgroundMinimal Residual Disease Detection: Implications for Clinical Diagnosis and Cancer Patient Treatment
Song, M., Pan, W., Yu, X., Ren, J., Tang, C., Chen, Z., Wang, Z., Deng, Y., He, N., Liu, H., et al. (2025) · MedComm · doi:10.1002/mco2.70193 · Cited by 23
“Clonal hematopoiesis is characterized by somatic mutations in hematopoietic stem cells present in the bone marrow, and patients who have undergone chemotherapy for nonhematologic malignancies have a high probability of subsequent myeloid malignancies [170–175].”
Unanticipated efficacy of SARS-CoV-2 vaccination in older adults
Pawelec, G., & McElhaney, J. E. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00219-y · Cited by 23
“Clearly, hematopoiesis may be so severely affected in the oldest old that it becomes essentially monoclonal, but what this means for immune status is not clear [17].”
BackgroundSchlegelberger, B., Mecucci, C., & Włodarski, M. W. (2021) · Familial Cancer · doi:10.1007/s10689-021-00263-z · Cited by 23
Valori, M., Jansson, L., & Tienari, P. J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0261002 · Cited by 22
Emerging Concepts of Vascular Cell Clonal Expansion in Atherosclerosis
Misra, A., Rehan, R., Lin, A., Patel, S., & Fisher, E. A. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316093 · Cited by 23
Voso, M. T., Pandzic, T., Falconi, G., Denčić‐Fekete, M., Bellis, E. D., Scarfò, L., Ljungström, V., Iskas, M., Poeta, G. D., Ranghetti, P., et al. (2022) · British Journal of Haematology · doi:10.1111/bjh.18129 · Cited by 25
Stem Cells, Hematopoiesis and Lineage Tracing: Transplantation-Centric Views and Beyond
Konturek-Cieśla, A., & Bryder, D. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.903528 · Cited by 24
Stelmach, P., Richter, S., Sauer, S., Fabre, M. A., Gu, M., Rohde, C., Janssen, M., Liebers, N., Proynova, R., Weinhold, N., et al. (2023) · Haematologica · doi:10.3324/haematol.2023.282992 · Cited by 23
“13,33 The biological consequences of PPM1D mutations in hematopoietic cells and how mutations in exon 6 of PPM1D confer a fi tness advantage to these cells in presence of chemotherapy have been comprehensively studied and there is strong evidence that PPM1D mutations improve HSC survival and result…”
BackgroundSikking, M. A., Stroeks, S. L. V. M., Henkens, M. T. H. M., Raafs, A. G., Cossins, B., van Deuren, R. C., Steehouwer, M., Riksen, N. P., van den Wijngaard, A., Brunner, H. G., et al. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2023.06.037 · Cited by 28
A pan-tissue survey of mosaic chromosomal alterations in 948 individuals
Gao, T., Kastriti, M. E., Ljungström, V., Heinzel, A., Tischler, A. S., Oberbauer, R. W., Loh, P., Adameyko, I. I., Park, P. J., & Kharchenko, P. V. (2023) · Nature Genetics · doi:10.1038/s41588-023-01537-1 · Cited by 24
Goldman, E. A., Spellman, P. T., & Agarwal, A. (2023) · Molecular Case Studies · doi:10.1101/mcs.a006251 · Cited by 25
“Under the tenets of Darwinian evolution, rapidly proliferating clonal cells outcompete their neighbors within their microenvironmental niche and can therefore achieve clonal dominance in the bloodstream (Jaiswal and Ebert 2019).”
InfluentialImmunometabolism in atherosclerotic disorders
Fleetwood, A. J., Noonan, J. E., Gruta, N. L. L., Kallies, A., & Murphy, A. J. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00473-5 · Cited by 28
“Hematopoietic aging, accelerated by chronic inflammation, increases myeloid cell production and enhances the risk of immune dysfunction and chronic disease development 129 .”
Ismail, W. M., Fernandez, J. A., Binder, M., Lasho, T. L., Kim, M., Geyer, S. M., Mazzone, A., Finke, C. M., Mangaonkar, A. A., Lee, J., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024014467 · Cited by 24
Ambrosi, T. H., Taheri, S., Chen, K., Sinha, R., Wang, Y., Hunt, E. J., Goodnough, L. H., Murphy, M. P., Steininger, H. M., Hoover, M. Y., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.02.013 · Cited by 27
Hematopoietic stem and progenitor cells as a reservoir for trained immunity
Tran, B. T., Jeyanathan, V., Cao, R., Kaufmann, E., & King, K. Y. (2025) · eLife · doi:10.7554/elife.106610 · Cited by 25
“…of a specific HSPC subset is reminiscent of clonal hematopoiesis of indeterminate potential (CHIP), a preleukemic condition in which the bone marrow of older individuals harbors an expanding population of cell clones with somatic mutations, often in cancer-driver genes ( Jaiswal and Ebert, 2019 ).”
Reversing lysosomal dysfunction restores youthful state in aged hematopoietic stem cells
Arif, T., Qiu, J., Khademian, H., Lohithakshan, A., Menon, A., Menon, V., Slavinsky, M., Batignes, M., Miao, L., Sebra, R., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.10.012 · Cited by 25
Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets
Zheng, P., Yan, W., Ding, Y.-N., Zhang, Y., Chen, Z., Qian, J., & Ge, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02630-7 · Cited by 26
“308 Moreover, epigenetic alterations not only affect gene expression but also induce cellular senescence and disrupt neurohormonal signaling pathways in the ageing cardiovascular system.”
Wudhikarn, K., Padrnos, L. J., Lasho, T. L., LaPlant, B. R., Kumar, S. K., Dispenzieri, A. A., Lacy, M. Q., Rajkumar, S. V., Gertz, M. A., Mangaonkar, A. A., et al. (2021) · American Journal of Hematology · doi:10.1002/ajh.26125 · Cited by 22
“CHIP is associated with an increased risk of developing MN and an increased all-cause mortality, largely due to cardiovascular disease.(3) The presence of CHIP prior to receiving chemotherapy and radiation has been associated with therapy related MN (T-MN), such as myelodysplastic syndromes (MDS) and acute myeloid leu…”
BackgroundMian, S. A., & Bonnet, D. A. (2021) · Cancers · doi:10.3390/cancers13164116 · Cited by 22
“Growing evidence suggests that ChIP itself may reflect certain aspects of the aging process [19,20], particularly in the BM tissue.”
BackgroundAldea, M. D., Tagliamento, M., Bayle, A., Vasseur, D., Vergé, V., Marinello, A., Danlos, F., Blanc‐Durand, F., Bernard, E., Cerbone, L., et al. (2023) · JCO Precision Oncology · doi:10.1200/po.22.00583 · Cited by 22
Kiladjian, J., & Cassinat, B. (2023) · American Journal of Hematology · doi:10.1002/ajh.26896 · Cited by 22
“hematopoiesis (ARCH), and for which the clinical significance remains to be precisely determined.(32,33) Altogether, the identification of one or several of these additional non-driver mutations may sometimes help for the diagnosis of an MPN, but their clinical and pathophysio-”
BackgroundNew insight into the causes, consequences, and correction of hematopoietic stem cell aging
Mansell, E., Lin, D. S. Y., Loughran, S. J., Milsom, M. D., & Trowbridge, J. J. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.07.002 · Cited by 21
de Andrade, K. C., Strande, N. T., Kim, J., Haley, J. S., Hatton, J. N., Frone, M. N., Khincha, P. P., Thone, G. M., Mirshahi, U. L., Schneider, C., et al. (2023) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2023.100242 · Cited by 26
Filipek-Gorzała, J., Kwiecińska, P., Szade, A., & Szade, K. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1308709 · Cited by 24
“The majority of CHIP cases are associated with mutations in DNMT3A, TET2 , and ASXL1 genes (49).”
Awada, H., Gurnari, C., Visconte, V., Durmaz, A., Kuzmanovic, T., Awada, H. K., Tu, Z. J., Cook, J. R., Bolwell, B. J., Sobecks, R. M., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02258-y · Cited by 27
“Further details are provided in the Data Supplement fi le.”
BackgroundKállai, A., Ungvari, Z. I., Fekete, M., Maier, A. B., Mikala, G., Andrikovics, H., & Lehoczki, A. (2024) · GeroScience · doi:10.1007/s11357-024-01374-y · Cited by 25
“CHIP is identified through genetic sequencing of blood cells, revealing specific mutations that confer a growth or survival advantage to particular cell clones [53, 54, 56, 92].”
Sill, H., Zebisch, A., & Haase, D. T. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2272 · Cited by 23
“Subjects with clonal hematopoiesis have an increased risk of hematologic malignancies, particularly therapyrelated myeloid neoplasms (13, 14).”
BackgroundSingle-cell multi-scale footprinting reveals the modular organization of DNA regulatory elementsPreprint
Hu, Y., Ma, S., Kartha, V. K., Duarte, F. M., Horlbeck, M. A., Zhang, R., Shrestha, R., Labade, A. S., Kletzien, H., Meliki, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.28.533945 · Cited by 22
A microglia clonal inflammatory disorder in Alzheimer’s disease
Vicario, R., Fragkogianni, S., Weber, L., Lazarov, T., Hu, Y., Hayashi, S. Y., Craddock, B., Socci, N. D., Alberdi, A., Baako, A., et al. (2025) · eLife · doi:10.7554/elife.96519.3 · Cited by 21
“This is consistent with recent studies showing that clonal hematopoiesis is associated with a higher risk of several diseases related to ageing such as cardiovascular diseases, but is inversely associated with the risk of AD ( Jaiswal and Ebert, 2019 ; Bouzid et al., 2023 ).”
Engineering Mice to Study Human Immunity
Sefik, E., Xiao, T., Chiorazzi, M., Odell, I. D., Zhang, F., Agrawal, K., Micevic, G., & Flavell, R. A. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-082523-124415 · Cited by 24
Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells
Wang, X., Wang, K., Zhang, W., Tang, Z., Zhang, H., Cheng, Y., Zhou, D., Zhang, C., Zhong, W., Ma, Q., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03540-7 · Cited by 21
“…cells (PBMC) samples of four young donors (aged 22–24 ) and obtained transcriptomics , chromatin accessibility and We also collected PBMC samples from two elderly donors (one male and one female) over 70 years old because clonal hematopoiesis were more frequently seen in elderly individuals [28].”
Protein phosphatase, Mg2+/Mn2+‐dependent 1D (PPM1D) mutations in haematological cancer
Husby, S., Justesen, E. H., & Grønbæk, K. (2020) · British Journal of Haematology · doi:10.1111/bjh.17120 · Cited by 21
“Furthermore, several studies conclude that larger clone sizes and higher number of mutations increase the risk of developing a haematological malignancy.(5) One of the genes mutated in CH is protein phosphatase, Mg/Mn-dependent 1D (PPM1D); a gene encoding a serine-threonine phosphatase called wild-type p53-induced pho…”
BackgroundDziadziuszko, R., Hung, T., Wang, K., Choeurng, V., Drilon, A. E. D. C., Doebele, R. C., Barlési, F., Wu, C., Dennis, L. M., Skoletsky, J., et al. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13214 · Cited by 21
Looking ahead: giant-cell arteritis in 10 years time
Bond, M., Tomelleri, A., Buttgereit, F., Matteson, E. L., & Dejaco, C. (2022) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x221096366 · Cited by 21
Applications of Liquid Biopsies in Non-Small-Cell Lung Cancer
Pešta, M., Shetti, D., Kulda, V., Knížková, T., Houfková, K., Bagheri, M. S., Svatoň, M., & Polívka, J. (2022) · Diagnostics · doi:10.3390/diagnostics12081799 · Cited by 21
Clonality in immune aplastic anemia: Mechanisms of immune escape or malignant transformation
Durrani, J., & Groarke, E. M. (2022) · Seminars in Hematology · doi:10.1053/j.seminhematol.2022.08.001 · Cited by 21
Kim, M. J., Song, H., Koh, Y., Lee, H., Park, H. E., Choi, S. H., Yoon, J. W., & Choi, S.-Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1181879 · Cited by 23
“The clonal expansion of hematopoietic cells with aging-related recurrent somatic mutations in the absence of other hematologic abnormalities is called clonal hematopoiesis of indeterminate potential (CHIP) (7).”
BackgroundKessler, M. D., Damask, A., O’Keeffe, S., Meter, M. V., Banerjee, N., Semrau, S., Li, D., Watanabe, K., Horowitz, J. E., Houvras, Y. J., et al. (2022) · medRxiv · doi:10.1101/2021.12.29.21268342 · Cited by 21
Moritz, J. M., Schwab, A., Reinisch, A., Zebisch, A., Sill, H., & Wölfler, A. (2024) · Biomedicines · doi:10.3390/biomedicines12030599 · Cited by 20
“Clonal hematopoiesis (CH) is characterized by the presence of somatic mutations of hematopoietic stem cells in the BM [63].”
BackgroundAcute myeloid leukaemia in patients we judge as being older and/or unfit
Lazarević, V. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13293 · Cited by 20
Kuhnert, S., Mansouri, S., Rieger, M. A., Savai, R., Avcı, E., Díaz-Piña, G., Padmasekar, M., Looso, M., Hadžić, S., Acker, T., et al. (2022) · Cells · doi:10.3390/cells11132121 · Cited by 20
Causes of Clonal Hematopoiesis: a Review
Joo, L., Bradley, C. C., Lin, S. H., Scheet, P. A., & Nead, K. T. (2023) · Current Oncology Reports · doi:10.1007/s11912-023-01362-z · Cited by 23
Mangaonkar, A. A., & Patnaik, M. M. (2023) · American Journal of Hematology · doi:10.1002/ajh.26915 · Cited by 20
Reconstructing phylogenetic trees from genome-wide somatic mutations in clonal samples
Coorens, T. H. H., Chapman, M. S., Williams, N., Martincorena, I., Stratton, M. R., Nangalia, J., & Campbell, P. J. (2024) · Nature Protocols · doi:10.1038/s41596-024-00962-8 · Cited by 24
“The detection of expanded clones in normal tissues has generally been limited to the detection of cancer-associated driver mutations, as has been the case with studies of clonal hematopoiesis 53 .”
Acute Myeloid Leukemia in Patients Living with HIV Infection: Several Questions, Fewer Answers
Forghieri, F., Nasillo, V., Bettelli, F., Pioli, V., Giusti, D., Gilioli, A., Mussini, C., Tagliafico, E., Trenti, T., Cossarizza, A., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031081 · Cited by 20
“5% to 1% per year, but also with cardiovascular diseases and all-cause mortality [50].”
BackgroundAn Unconventional View of T Cell Reconstitution After Allogeneic Hematopoietic Cell Transplantation
Andrlová, H., van den Brink, M. R. M., & Markey, K. A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.608923 · Cited by 21
“influence clonal hematopoiesis (CH)—a recently definedcondition, which represents a pre-leukemic state (27).”
BackgroundSingle-Cell Epigenomics Reveals Mechanisms of Cancer Progression
LaFave, L. M., Savage, R. E., & Buenrostro, J. D. (2022) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-070620-094453 · Cited by 20
Pianko, M. J., & Golob, J. L. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10033-7 · Cited by 20
“Clonal hematopoiesis (CH) driven by mutations in myeloid transcription factors such as DNMT3A and TET2 becomes more common with age and is associated with increased expression of pro-inflammatory cytokines and contributes to inflammaging [89].”
BackgroundAll that glitters is not LGL Leukemia
Semenzato, G., Teramo, A., Calabretto, G., Gasparini, V. R., & Zambello, R. (2022) · Leukemia · doi:10.1038/s41375-022-01695-x · Cited by 22
“Approximately 10% of persons older than 70 years [23, 24, 26], and 30% older than 80 [27], carry these lesions with DNMT3A, TET2 and ASXL1 being the most commonly mutated genes.”
BackgroundGu, W., Zhang, Y., Sun, T., Ju, M., Liu, X. F., Xue, F., Chen, Y., Liu, W., Zhang, D., Huiyuan, L., et al. (2023) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2023.100132 · Cited by 19
“Interestingly, those epigenetic regulators DNMT3A and ASXL1 accounted for more than half of the clonal hematopoiesis of indeterminate potential (CHIP) [30].”
BackgroundInfluentialDecoding functional hematopoietic progenitor cells in the adult human lung
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. (2025) · Blood · doi:10.1182/blood.2024027884 · Cited by 25
Clonal Evolution of PPM1D Mutations in the Spectrum of Myeloid Disorders
Fandrei, D., Pegliasco, J., Pasquier, F., Ibrahim, N., Kfoury, M., Berthon, C., Heiblig, M., Lebon, D., Marçais, A., Meunier, M., et al. (2025) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-3683 · Cited by 19
Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging
Pham, J., Isquith, J. M., Balaian, L., Nandi, S. P., Engstrom, C., Mack, K., van der Werf, I. M., Chang, P. C., Stoudemire, J., Ladel, L., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.07.013 · Cited by 18
“14 23 Finally, stress and environmental toxin-induced genomic instability contribute to the acquisition of clonal hematopoietic (CH) mutations 24 that can promote malignant transformation of pre-leukemia stem cells (pre-LSCs) into therapy-resistant LSCs in acute myeloid leukemia (AML).”
Drozd, M., Pujades‐Rodríguez, M., Morgan, A. W., Lillie, P. J., Witte, K. K., Kearney, M. T., & Cubbon, R. M. (2022) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiac186 · Cited by 19
“It is notable that recent data have suggested that clonal hematopoiesis of indeterminate potential, a disorder arising from somatic mutations that promote overrepresentation of proinflammatory myeloid clones (and elevated CRP) [29, 30], is associated with increased risk of diverse infections [31].”
BackgroundTargeting stem cells in myelodysplastic syndromes and acute myeloid leukemia
Woll, P. S., Yoshizato, T., Hellström‐Lindberg, E., Fioretos, T., Ebert, B. L., & Jacobsen, S. E. W. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13535 · Cited by 15
Self-citationPresent and Future Role of Immune Targets in Acute Myeloid Leukemia
Damiani, D., & Tiribelli, M. (2022) · Cancers · doi:10.3390/cancers15010253 · Cited by 19
Crisafulli, E., Sartori, G., Vianello, A., Busti, F., Nobili, A., Mannucci, P. M., Girelli, D., REPOSI Investigators, Mannucci, P. M., Sesti, G., et al. (2023) · Internal and Emergency Medicine · doi:10.1007/s11739-023-03207-w · Cited by 19
“Furthermore, in the last few years HF has been consistently associated with the presence of clonal hemopoiesis of indeterminate potential (CHIP), a common age-related phenomenon characterized by the presence of somatic mutations in clonal leukocytes that are able to drive an aberrant inflammatory response [35].”
BackgroundHigh-risk and silent clonal hematopoietic genotypes in patients with nonhematologic cancer
Stonestrom, A. J., Menghrajani, K. N., Devlin, S. M., Franch‐Expósito, S., Ptashkin, R. N., Patel, S. Y., Spitzer, B. G., Wu, X., Jee, J., Vela, P. S., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023011262 · Cited by 18
Li, Z., Huang, W., Yin, J. C., Na, C., Wu, X., Shao, Y. W., Ding, H., & Li, J. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.222 · Cited by 18
Hiding in Plain Sight — Somatic Mutation in Human Disease
Levy‐Lahad, E., & King, M. (2020) · New England Journal of Medicine · doi:10.1056/nejme2030754 · Cited by 18
Somatic mosaicism in genetic errors of immunity
Cooper, M. A. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.11.038 · Cited by 21
Identifying genetic errors of immunity due to mosaicism
Schmitz, E. G., Griffith, M., Griffith, O. L., & Cooper, M. A. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20241045 · Cited by 19
Early detection and intervention of clonal hematopoiesis for preventing hematological malignancies
Ye, B., Sheng, Y., Zhang, M., Hu, Y., & Huang, H. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215691 · Cited by 17
Bagnara, D., Mazzarello, A. N., Ghiotto, F., Colombo, M., Cutrona, G., Fais, F., & Ferrarini, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214249 · Cited by 17
Cancer cytogenetics in a genomics world: Wedding the old with the new
Balciuniene, J., Ning, Y., Lazarus, H. M., Aikawa, V., Sherpa, S., Zhang, Y., & Morrissette, J. J. D. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101209 · Cited by 17
Inflammation in myelodysplastic syndrome pathogenesis
Rodríguez‐Sevilla, J. J., & Colla, S. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.09.005 · Cited by 20
Clonal Hematopoiesis of Indeterminate Potential as a Novel Risk Factor for Donor-Derived Leukemia
Burns, S. S., & Kapur, R. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.07.008 · Cited by 19
“Thesemutations can endow a subpopulation of these cells with a growth advantage (Jaiswal and Ebert, 2019).”
BackgroundYung, Y., Lee, E., Chu, H.-T., Yip, P.-K., & Gill, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020659 · Cited by 22
Pedersen, R. K., Andersen, M., Stiehl, T., & Ottesen, J. T. (2021) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2021.110620 · Cited by 17
Precocious clonal hematopoiesis in Down syndrome is accompanied by immune dysregulation
Liggett, L. A., Galbraith, M. D., Smith, K. P., Sullivan, K. D., Granrath, R. E., Estrada, B. A. E., Kinning, K. T., Shaw, J. R., Rachubinski, A. L., Espinosa, J. M., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003858 · Cited by 17
“This interplay is evident in clonal hematopoiesis (CH), in which human hematopoietic stem and progenitor cells acquire driver mutations that promote their clonal expansion.(1) Although hematopoietic clonality is rare in young people, the incidence dramatically increases after midlife.”
BackgroundInfluentialNewell, L. F., Dunlap, J. B., Gatter, K. M., Bagby, G. C., Press, R. D., Cook, R. J., Fletcher, L. B., Leonard, J. T., Leong, K., Bubalo, J. S., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16635 · Cited by 17
Camus, V., Viennot, M., Lévêque, É., Viailly, P., Tonnelet, D., Veresezan, E., Drieux, F., Etancelin, P., Dubois, S., Stamatoullas, A., et al. (2022) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2021.2010060 · Cited by 17
“However, CHIP has been mainly described with genes such as TET2 [49], DNMT3A [50], and TP53 [51], which were not included in our panel and are instead reported in cohorts of elderly patients [52], while our PMBL population was young.”
MethodAljoufi, A., Zhang, C., Ropa, J. P., Chang, W., Palam, L. R., Cooper, S. H., Ramdas, B., Capitano, M. L., Broxmeyer, H. E., & Kapur, R. (2022) · Blood · doi:10.1182/blood.2022015499 · Cited by 20
A cellular identity crisis? Plasticity changes during aging and rejuvenationPreprint
Gorelov, R. A., & Hochedlinger, K. (2024) · Genes & Development · doi:10.1101/gad.351728.124 · Cited by 18
“Although this topic has been extensively reviewed elsewhere, it remains a striking example of how an age-associated process — in this case, the accrual of mutations — can lead cells to enter a preneoplastic state (Jaiswal and Ebert 2019; Kapadia and Goodell 2024).”
Clonal hematopoiesis is associated with distinct rheumatoid arthritis phenotypes
Hiitola, E., Korhonen, J., Kokkonen, H., Koskela, J. T., Kankainen, M., Alakuijala, M., Liu, A., Lundgren, S., Häppölä, P., Almusa, H., et al. (2025) · Science Advances · doi:10.1126/sciadv.adt9846 · Cited by 18
“The role of aging-related clonal hematopoiesis (CH) in inflammatory diseases remains to be fully characterized ( 1 , 2 ).”
Dhillon, V. S., Deo, P., Bonassi, S., & Fenech, M. F. (2021) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2021.108372 · Cited by 16
Qiu, X. Y., Dai, Y., Cheng, S., Gu, H., Jiang, Y., Meng, X., Wang, Y., Zhao, X., Jiang, Y., Xu, Z., et al. (2022) · Stroke and Vascular Neurology · doi:10.1136/svn-2022-001756 · Cited by 16
“Further study to investigate this issue in a larger scale cohort will be conducted in future work.”
Elective genomic testing: Practice resource of the National Society of Genetic Counselors
Zawatsky, C. L. B., Bick, D. P., Bier, L., Funke, B., Lebo, M. S., Lewis, K. L., Orlova, E., Qian, E., Ryan, L. A., Schwartz, M. L. B., et al. (2023) · Journal of Genetic Counseling · doi:10.1002/jgc4.1654 · Cited by 19
Relationships Between Regeneration, Wound Healing, and Cancer
Maggiore, G., & Zhu, H. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-123558 · Cited by 18
Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation
Woo, K. A., Kim, H., Lee, C. Y., Shin, J. H., Sun, C.-H., Im, H., An, H., Lim, J., Choi, S., Koh, Y., et al. (2024) · npj Parkinson s Disease · doi:10.1038/s41531-024-00784-1 · Cited by 16
“While multiple studies set the CHIP threshold at 2.0, varying thresholds such as 1.0%, 2.0%, and 5.0% arealsoutilizeddependingonthediseasecontext,testingfacility,andcohort characteristics 5 .”
InfluentialUBA1 dysfunction in VEXAS and cancer
Sakuma, M., Haferlach, T., & Walter, W. (2024) · Oncotarget · doi:10.18632/oncotarget.28646 · Cited by 16
Sun, Y., Yu, Y., Cai, L., Yu, B., Xiao, W., Tan, X. W., Wang, Y., Lu, Y., & Wang, N. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02626-7 · Cited by 20
“Concurrently, aging contributes to the accumulation of mutations in somatic cells, with CHIP serving as a hallmark of aging [36], which suggests the necessity of exploring the relationship between CHIP and CVD risk in the diabetic population.”
The rewired immune microenvironment in leukemia
Ciantra, Z. B., Paraskevopoulou, V., & Aifantis, I. (2025) · Nature Immunology · doi:10.1038/s41590-025-02096-9 · Cited by 19
“Conditions associated with inflammation, notably aging, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and infection, are risk factors in the development of both chronic and acute leukemias 151 .”
Buono, M. F., Benavente, E. D., Daniels, M., Mol, B. M., Mekke, J. M., de Borst, G. J., de Kleijn, D. P. V., van der Laan, S. W., Pasterkamp, G., Onland‐Moret, N. C., et al. (2023) · Biology of Sex Differences · doi:10.1186/s13293-023-00527-6 · Cited by 17
The Muller’s Ratchet and Aging
Govindaraju, D. R., Innan, H., & Veitia, R. A. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.02.004 · Cited by 17
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“Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of developing blood cancer, in particular MDS/AML, and it likely represents a precancerous clonal expansion with a high potential to progress to malignant hematological diseases.(25) Currently, there are no published data addre…”
BackgroundSingle-cell genotype-phenotype mapping identifies therapeutic vulnerabilities in VEXAS syndromePreprint
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“The presence of CHIP has been associated with an increased risk of atherosclerosis, thrombogenesis, cardiovascular disease, acute kidney injury, and the development of hematologic malignancies (1, 4, 11, 12).”
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Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?
Piccirillo, N., Putzulu, R., Metafuni, E., Massini, G., Fatone, F., Corbingi, A., Giammarco, S., Limongiello, M. A., Giovanni, A. D., Zini, G., et al. (2023) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2023.150725 · Cited by 15
Characterization and Optimization of Multiomic Single-Cell Epigenomic Profiling
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Immune Aging and Its Implication for Age-Related Disease Progression
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Thrombotic, Vascular, and Bleeding Complications of the Myeloproliferative Neoplasms
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van Deuren, R. C., Andersson-Assarsson, J. C., Kristensson, F. M., Steehouwer, M., Sjöholm, K., Svensson, P.-A., Pieterse, M., Gilissen, C., Taube, M., Jacobson, P., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.12.443095 · Cited by 15
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The landscape and evolution of clonal hematopoiesis in chronic lymphocytic leukemia
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Metadata
- Authors
- Jaiswal, S., & Ebert, B. L.
- Affiliations
- Stanford Medicine (US)
- Broad Institute (US)
- Corresponding author
- Jaiswal, Siddhartha
- Ebert, Benjamin L.
- Venue
- Science
- Published
- 2019-11
- Volume
- 366
- Issue
- 6465
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8050831
- OpenAlex
- W2982291252
- Semantic Scholar
- 6d1a7a80dacac969118008d44a082733bff68245
- Cited by
- 1,156
- References
- 98
- Citations by year
- 2026: 173 · 2025: 222 · 2024: 206 · 2023: 169 · 2022: 164 · 2021: 136 · 2020: 83 · 2019: 3
- FWCI
- 15.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Japanese Society of Hematology
- Funders
- National Institutes of Health (P01CA066996, P50CA206963, R01HL082945)
- Burroughs Wellcome Fund
- Edward P. Evans Foundation
- Ludwig Institute for Cancer Research
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- clonal hematopoiesis, somatic mutations, aging, hematopoietic stem cells, cancer risk, immune function
- MeSH terms
- Aged, Aging, Animals, Cardiovascular Diseases, Clone Cells, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mutation, Precancerous Conditions, Hematologic Neoplasms, Clonal Evolution
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