The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index; 6 of the 124 sources its claims cite were checked for support.
Clonal hematopoiesis in human aging and disease
Open accessAbstract
Cryptic signs of aging in our blood: Time is not a friend to our DNA. Aging is associated with an accumulation of somatic mutations in normal dividing cells, including the hematopoietic stem cells (HSCs) that give rise to all blood cells. Certain mutations in HSCs confer a fitness advantage that results in clonal expansions of mutant blood cells that sometimes—but not always—forecast the development of cancer and other age-related diseases. Jaiswal and Ebert review this process of “clonal hematopoiesis,” including the mechanisms by which it arises and the current state of knowledge regarding its effects on human health. Science , this issue p. eaan4673
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Clonal hematopoiesis, especially CHIP, is common with aging and driven largely by DNMT3A/TET2 mutations; it raises risk of blood cancers, cardiovascular disease, and mortality. Mouse and human data support causal roles in atherosclerosis and inflammation, though mechanisms and broader disease links remain uncertain.
Key findings
- Clonal hematopoiesis is age-related: detectable in <1% of healthy individuals under age 40 but 10–20% of those age 70 or older; in one study, a median of ~18% of blood cells carried the mutations. Nearly two-thirds of clonal hematopoiesis was accounted for by loss-of-function mutations in DNMT3A and TET2, with ASXL1 third most common.
- CHIP was associated with ~10-fold increased relative risk of hematological malignancies; 4% of CHIP carriers developed a blood cancer over 8 years, corresponding to ~0.5% conversion per year. Nested case-control studies found ~3- to 5-fold increased AML risk.
- CHIP was associated with a 30–40% increased mortality risk and increased cardiovascular risk: coronary heart disease and ischemic stroke risk more than doubled, early-onset MI risk was four times higher, and JAK2 mutations conferred ~12-fold higher coronary heart disease risk and ~12-fold venous thrombosis risk.
- Mouse models showed that Tet2 or Dnmt3a loss accelerates atherosclerosis and heart failure, with IL-1B blockade reversing accelerated atherosclerosis; CHIP genes also affect inflammatory pathways including IL6 and IL8.
Methods
- Narrative review; no primary data collection or formal meta-analysis.
- Synthesizes human population and exome sequencing studies, including cohorts of greater than 30,000 persons, nested case-control studies, and mouse models.
- Main analysis is qualitative synthesis of genetic associations, clinical outcomes, and mechanistic experiments.
Limitations
- Stated: mechanisms by which DNMT3A/TET2 and splicing factor mutations drive clonal expansion remain unclear; causality for non-malignant diseases beyond cardiovascular disease is not established, with type 2 diabetes possibly reflecting reverse causation and COPD potentially confounded by smoking.
- Stated: prevalence estimates depend heavily on detection sensitivity, and the biological significance of smaller clones is unknown; clone trajectories vary between people and risk stratification remains incomplete.
- Evident: as a narrative review, it lacks systematic search or quality assessment and provides no new primary data; risk estimates are drawn from heterogeneous studies.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
77 Not checked yet · 26 Own interpretation · 20 No basis given · 5 Own result · 3 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“also found that Il1b, IL8 family chemokines, and other inflammatory mediators show increased expression in Tet2-deficient macrophages challenged with low-density lipoprotein or endotoxin 79,86,92”
§ Clonal hematopoiesis in human aging and disease > Immune function and CHIP
What the sources say
- Supportedcites [79] Jaiswal S Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med 377, 111– 121, doi: 10.1056/NEJMoa1701719 (2017). 28636844 PMC6717509 source
The Results section reports increased Il1b and CXC chemokine transcripts in Tet2-deficient macrophages exposed to LDL, and greater secretion of inflammatory proteins after LDL loading or endotoxin exposure than in controls. It qualifies that endotoxin, but not LDL, caused robust Il1b secretion. (LLM, conf=0.90)
- Partly supportedcites [86] Fuster JJ Clonal hematopoiesis associated with Tet2 deficiency accelerates atherosclerosis development in mice. Science, doi: 10.1126/science.aag1381 (2017). PMC5542057 28104796 sourceExperimental — accuracy not yet measured
The paper’s Abstract reports increased Il1b expression and broader cytokine and chemokine expression in TET2-deficient macrophages treated with LPS/IFN-γ. But under oxLDL/TNF/IFN-γ stimulation, it says the effect on other cytokines and chemokines was minimized, with IL-1β the exception. The passages do not specifically identify IL8-family chemokines as increased, so the claim overgeneralizes across the two challenges. (LLM, conf=0.88)
- Not checked yetcites [92] Cull AH, Snetsinger B, Buckstein R, Wells RA & Rauh MJ Tet2 restrains inflammatory gene expression in macrophages. Exp Hematol 55, 56– 70 e13, doi: 10.1016/j.exphem.2017.08.001 (2017). 28826859 source
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other studies have found links between CHIP and chronic obstructive pulmonary disease (COPD) 37,63.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
The section “Association of CH with other phenotypes” reports a significant association between clonal hematopoiesis and chronic pulmonary disease, but does not identify that disease category specifically as COPD (page unavailable). In “Association of germline TERT variants with CH,” COPD appears only as a covariate in a separate telomere-length analysis, not as a reported CH–COPD association. (LLM, conf=0.86)
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
In “Risk factors for acquiring mutations,” the paper reports a significant association between TET2 mutations and self-reported COPD-asthma. The Discussion likewise describes an association with self-reported asthma-COPD. This supports a qualified link, but the paper does not establish an association with COPD alone or with CHIP irrespective of mutation type. (LLM, conf=0.87)
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.
- Partly supported
In the paper
“As each HSC acquires ~1 exonic mutation per decade of life 3,”
§ Clonal hematopoiesis in human aging and disease > Introduction
What the sources say
- Not checked yetcites [3] Welch JS The origin and evolution of mutations in acute myeloid leukemia. Cell 150, 264– 278, doi: 10.1016/j.cell.2012.06.023 (2012). 22817890 PMC3407563 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- 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.
In the paper
“But in the 1990s, studies of non-random X-chromosome inactivation (XCI) in women led to the discovery that clonal hematopoiesis also occurs in individuals without cancer 18.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [18] Fey MF Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe. Blood 83, 931– 938 (1994). 8111064 source
plaindirect- Asserted: passes — The authors put it forward as true.
- 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.
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
“The surprising result of this experiment of nature was that clonal hematopoiesis largely results from mutations in a very restricted set of genes.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaindirect- Asserted: passes — The authors put it forward as true.
- 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.
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
“This outgrowth, called “clonal hematopoiesis,” is highly prevalent in the elderly population.”
- Also stated in: § Introduction · boosted
“Indeed, numerous studies have now shown that such outgrowths of mutated blood cells, termed “clonal hematopoiesis,” are highly prevalent in the elderly.”
§ Clonal hematopoiesis in human aging and disease > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- 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.
- Also stated in: § Introduction · boosted
In the paper
“Importantly, non-random XCI in blood cells was observed to increase in frequency with age, although the underlying mechanism was unclear 19.”
§ Clonal hematopoiesis in human aging and disease > A brief history of clonal hematopoiesis
What the sources say
- Not checked yetcites [19] Champion KM, Gilbert JG, Asimakopoulos FA, Hinshelwood S & Green AR Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes. British journal of haematology 97, 920– 926 (1997). 9217198 source
plaindirect- Asserted: passes — The authors put it forward as true.
- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The third most commonly mutated gene was ASXL1, a chromatin regulator, while mutations in splicing factors (SF3B1, SRSF2, PRPF8, U2AF1) were also frequent.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaincorrelational- Asserted: passes — The authors put it forward as true.
- 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.
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.
- 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.
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.
- 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. 31
- Probably not a substantial claim. 18
The cited sources support only part of this claim — read each source’s verdict below.
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
- Supportedcites [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
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“An equivalent state is also pervasive in the epithelium of skin 14 and esophagus 15,16, suggesting that somatic mutation-driven clonal expansions may be a characteristic of aging in several tissues.”
§ Clonal hematopoiesis in human aging and disease > Introduction
What the sources say
- Not checked yetcites [14] Martincorena I Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880– 886, doi: 10.1126/science.aaa6806 (2015). 25999502 PMC4471149 source
- Not checked yetcites [15] Martincorena I Somatic mutant clones colonize the human esophagus with age. Science 362, 911– 917, doi: 10.1126/science.aau3879 (2018). 30337457 PMC6298579 source
- Not checked yetcites [16] Yokoyama A Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565, 312– 317, doi: 10.1038/s41586-018-0811-x (2019). 30602793 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“by the age of 70 an average person would be expected to harbor up to 1.4 million protein-coding variants, corresponding to an average of 70 mutations per gene, in at least one HSC (Fig. 1).”
§ Clonal hematopoiesis in human aging and disease > Introduction
hedged- Asserted: passes — The authors put it forward as true.
- 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
“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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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
“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.
- 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. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Somatic clones were detectable in less than 1% of healthy individuals under age 40, but they increased in frequency with each decade of life.”
§ Clonal hematopoiesis in human aging and disease > Clonal hematopoiesis in the genome sequencing era
plaincorrelational- Asserted: passes — The authors put it forward as true.
- 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
“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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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
“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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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.
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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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.
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.
- 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
“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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Loss of some of these proteins may allow for immune escape, thus explaining selection for PIGA-mutated clones.”
§ Clonal hematopoiesis in human aging and disease > Mechanisms of clonal expansion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says 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
“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.
- 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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Subsequent studies showed that loss of Tet2 or Dnmt3a led to worsening heart function in a mouse model of congestive heart failure, corroborating the human genetic association 87,88.”
§ Clonal hematopoiesis in human aging and disease > CHIP and non-malignant disease
What the sources say
- Not checked yetcites [87] Sano S CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease. Circ Res 123, 335– 341, doi: 10.1161/CIRCRESAHA.118.313225 (2018). 29728415 PMC6054544 source
- Not checked yetcites [88] Sano S Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1beta/NLRP3 Inflammasome. J Am Coll Cardiol 71, 875– 886, doi: 10.1016/j.jacc.2017.12.037 (2018). 29471939 PMC5828038 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies indicate that CHIP in the setting of other cancers is likely to be especially pervasive and portends a poor prognosis.”
§ Clonal hematopoiesis in human aging and disease > CHIP and hematological malignancy
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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
“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]
The 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]
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 601–700 of 1,000
Mutation-dependent responses to sleep and exercise in clonal haematopoiesis
Gerhardt, T., Jacob, W., Gaebel, L., Heiser, M., Wolfram, C., Huynh, P., Nakao, T., dos Santos, B. G., Toh, P., Douglas, A., et al. (2026) · Nature · doi:10.1038/s41586-026-10634-0 · Cited by 10
Wei, Y., Kanagal‐Shamanna, R., Zheng, H., Bao, N., Lockyer, P. P., Class, C. A., Darbaniyan, F., Lü, Y., Lin, K., Yang, H., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01605-1 · Cited by 6
“5–1% of individuals with CHIP will develop a hematopoietic malignancy per year [7], suggesting that during the course of aging only some of the TET2 mutant clones gain an advantage that results in clonal evolution and expansion eventually resulting in hematological disorders such as CMML.”
BackgroundThe research progress of targeted therapy in acute myeloid leukemia based on bibliometric analysis
Huang, W., Sun, G., Wang, Q., & Long, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.957370 · Cited by 7
“The results indicated that individuals with antecedent CH had an approximately ~3- to 5-fold increased risk of developing AML in subsequent years (72).”
BackgroundQiu, Y., & Zhao, W. (2024) · The Innovation Medicine · doi:10.59717/j.xinn-med.2023.100048 · Cited by 6
Ghezelayagh, T., Kohrn, B. F., Fredrickson, J., Krimmel-Morrison, J. D., Latorre-Esteves, E., Tee, X., Radke, M., Manhardt, E., Norquist, B., Katz, R., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03089-y · Cited by 5
“Aside from the connection between CHIP and AML [36] however, little is known about whether mutations in cancer driver genes within otherwise normal cells are related to the development of cancer.”
Competition shapes the landscape of X-chromosome-linked genetic diversity
Buenaventura, T., Bagci, H., Patrascan, I., Graham, J. J., Hipwell, K. D., Oldenkamp, R., King, J. W. D., Urtasun-Elizari, J., Young, G. R., Mouzo, D., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01840-5 · Cited by 6
Xi, Z., Feng, H., Chen, K., Guo, X., Zhu, D., Zheng, J., & Li, Y. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102242 · Cited by 6
Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease
Zhang, X. J., Wang, Y., Xue, H., Zhao, Y., Liu, M.-C., Wei, H., & Liu, Q. (2025) · BMC Medicine · doi:10.1186/s12916-025-04077-z · Cited by 6
“It is well documented that CHIP might evoke pro-inflammatory effects and alter the immune effector cells’ function [12–17].”
Mantle cell lymphoma and the evidence of an immature lymphoid component
Hansen, S. V., Nyvold, C. G., & Hansen, M. H. (2022) · Leukemia Research · doi:10.1016/j.leukres.2022.106824 · Cited by 6
The Field of Cell Competition Comes of Age: Semantics and Technological Synergy
Maheden, K., Zhang, V. W., & Shakiba, N. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.891569 · Cited by 7
“Haematopoietic stem cell populations tend towards clonality in an age-dependent manner (Genovese et al., 2014; Jaiswal and Ebert, 2019; Silver et al., 2021).”
BackgroundHuman adult hippocampal neurogenesis is back, again?
Liu, H. (2022) · Cell Research · doi:10.1038/s41422-022-00698-8 · Cited by 6
Clinical manifestations of clonal hematopoiesis: What has SF3B1-mutant MDS taught us?
Todisco, G., Moura, P. L., & Hellström‐Lindberg, E. (2022) · Seminars in Hematology · doi:10.1053/j.seminhematol.2022.08.002 · Cited by 5
Amador, C. C., Cook, J. R., Czader, M., Duffield, A. S., Goodlad, J. R., Nejati, R., Ott, G., Xiao, W., Davé, S. S., Wasik, M. A., et al. (2023) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqad045 · Cited by 6
Yu, C., Sheng, Y., Yu, F., Ni, H., Qiu, A., Huang, Y., & Qian, Z. (2023) · Journal of Clinical Investigation · doi:10.1172/jci163911 · Cited by 7
Molecular Studies for the Early Detection of Philadelphia-Negative Myeloproliferative Neoplasms
Stuckey, R., Bilbao, C., Segura-Díaz, A., & Gómez‐Casares, M. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612700 · Cited by 6
“In this way, if the genetic alterations affect genes important in hematopoiesis, they may provide a selective advantage to the cell, resulting in clonal hematopoiesis [27,28].”
BackgroundFulvio, G., Baldini, C., Mosca, M., Paolo, A. D., Bocci, G., Palumbo, G. A., Cacciola, E., Migliorini, P., Cacciola, R. R., & Galimberti, S. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1254868 · Cited by 7
“CHIP is characterized by the presence of clonal mutation with an allelic frequency > 2% in peripheral blood, without dysplasia, overt hematological neoplasms, or abnormalities in blood cell count, which represents a risk factor for myelodysplasia and leukemia (19–21).”
BackgroundPagliuca, S., & Ferraro, F. (2024) · Seminars in Hematology · doi:10.1053/j.seminhematol.2024.01.002 · Cited by 6
Gao, L., Yang, L., Zhou, S., Zhu, W., Han, Y., Chen, S., Xue, S., Wang, Y., Qiu, H., Wu, D., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03640-4 · Cited by 6
“Overall, better performance in MUDs was likely due to relatively younger donors as stated in a previous review that cumulative incidences of indeterminate mutations or impairments in blood stem cells with increasing age have the potential to impact clonal expansion or even denote a malignancy [36].”
ResultAuberle, C., Gao, F., Sloan, J. M., Morgensztern, D., Winkler, L., Ward, J. P., Devarakonda, S. H. K., Rearden, T. P., Govindan, R., & Waqar, S. N. (2024) · Journal of Thoracic Disease · doi:10.21037/jtd-23-1717 · Cited by 6
“Mutations in DNA damage response genes, such as TP53 , are more common in solid tumor malignancies than hematologic malignancies (33).”
BackgroundHe, H., Wen, Y., Yu, H., Liu, J., Huo, Q., Jin, W., Wang, Z., Du, G., Du, J., Wang, H., et al. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101397 · Cited by 5
Epidemiology and Etiology of AML
Juliusson, G., Lehmann, S., & Lazarević, V. (2021) · Hematologic malignancies · doi:10.1007/978-3-030-72676-8_1 · Cited by 6
Mature T-cell and NK-cell lymphomas: updates on molecular genetic features
Lewis, N. E., Sardana, R., & Doǧan, A. (2023) · International Journal of Hematology · doi:10.1007/s12185-023-03537-7 · Cited by 6
“Indeed, identical lymphoma-associated TET2 and DNMT3A mutations occur frequently in additional cell populations in AITL patients, including early HSP, myeloid, B-, and other T-cells, strongly suggesting those mutations occur in early pluripotent HSPCs, while other mutations (e.g., RHOA, IDH2, VAV1, PLCG1, CD28) are on…”
BackgroundClonal Hematopoiesis and Cardiovascular Diseases: The Connection
Mozzini, C., & Pagani, M. (2021) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2021.100962 · Cited by 7
Clonal hematopoiesis in sickle cell diseasePreprint
Liggett, L. A., Cato, L. D., Weinstock, J. S., Zhang, Y., Nouraie, M. S., Gladwin, M. T., Garrett, M. E., Ashley‐Koch, A. E., Telen, M. J., Custer, B., et al. (2021) · medRxiv · doi:10.1101/2021.06.12.21258772 · Cited by 6
Hungry for biomarkers of aging
LeBrasseur, N. K. (2024) · Aging Cell · doi:10.1111/acel.14158 · Cited by 6
“Indeed, biomarkers of senescence, mitochondrial dysfunction, DNA meth - ylation, somatic mutations, and other hallmarks have shown potential for predicting risk for adverse events in older adults (Fielding et al., 2023 ; Jaiswal & Ebert, 2019; Mahapatra et al., 2023 ; McCrory et al., 2021).”
BackgroundThe dynamic fitness landscape of ageing haematopoiesis through clonal competitionPreprint
Père, N. V. M., Terenzi, F., & Werner, B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.16.589764 · Cited by 6
“We implemented the clonal competition model with accumulation of neutral mutations as a Moran model [14] via the stochastic simulation algorithm (SSA, also referred to as the Gillespie algorithm [15]).”
Methylation clocks fail to generalize across genetically admixed individualsPreprint
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:10.7554/elife.105343 · Cited by 7
“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 Mutations Increase Risk of Alzheimer’s Disease with APOE ε3/ε3 Genotype
Choi, J., Park, K. S., Le Guen, Y., Park, J.-H., Zhou, Z., Enyenihi, L., Rosen, I., Choi, Y.-H., Walsh, C. A., Kim, J.-W., et al. (2025) · doi:10.1101/2025.05.19.654981 · Cited by 5
Protocol for mitochondrial variant enrichment from single-cell RNA sequencing using MAESTER
Good, J., Safina, K. R., Miller, T. E., & van Galen, P. (2025) · STAR Protocols · doi:10.1016/j.xpro.2024.103564 · Cited by 5
Emergence of CpG-cluster blanket methylation in aged tissues: a novel signature of epigenomic aging
Kang, Y., Min, B., Eom, J., Park, J. S., Jang, J., & Jeong, S. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf354 · Cited by 7
“We direct our attention to studies on CHIP (clonal haematopoiesis of indeterminate potential [ 70 ]), which is characterized by the expansion of haematopoietic stem cells bearing somatic mutations, most often in the DNMT3A and TET2 genes [ 71 ].”
Thymic pioneers: Charting the origin, identity, and fate of human thymus seeding progenitors
Liang, K. L., Boehme, L., Paepens, S., Hassan, M., & Taghon, T. (2025) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2025.06.014 · Cited by 6
Genomic landscape of radiation-induced somatic mutations in a normal cell
Matsuda, Y., & Tanabe, O. (2025) · Carcinogenesis · doi:10.1093/carcin/bgaf044 · Cited by 5
“[26].”
Genomic Perspective on Heterogeneity of Organs and Body Aging
Salimi, S., Raftery, D., & Ferrucci, L. (2026) · Aging Cell · doi:10.1111/acel.70353 · Cited by 8
Modeling the evolutionary dynamics of clonal hematopoiesis
Marzban, S., Stiehl, T., Xie, Z., Andersen, M., Snyder, J. A., Gudmand‐Hoeyer, J., Ottesen, J. T., Père, N. V. M., Werner, B., Huang, W., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02504-2 · Cited by 7
Integrating germline and tumor sequencing to improve hereditary cancer diagnosis and care
de Voer, R. M., & Valle, L. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-026-02046-5 · Cited by 5
“47 – 49 ).”
Somatic mutations reveal the ontogeny of microglia in human ageing
Belk, J. A., Zhang, Y., Reilly, E., Shi, Q., Liu, D. D., Womack-Gambrel, N., van der Linde, M., Ma, L., Paul, D., Enciso, A. M., et al. (2026) · Nature · doi:10.1038/s41586-026-10939-0 · Cited by 13
“Clonal expansions become ubiquitous during ageing 11–14, 33–”
Self-citationThe utility of liquid biopsy in clinical genetic diagnosis of cancer and monogenic mosaic disorders
Hallermayr, A., Keßler, T., Steinke‐Lange, V., Heitzer, E., Holinski‐Feder, E., & Speicher, M. R. (2023) · Medizinische Genetik · doi:10.1515/medgen-2023-2066 · Cited by 5
“Further, an association of CHIP with nonma-lignant disorders has been described since immune cells are not locally restricted but can migrate to and influence almost all organs [42].”
BackgroundIncreased TP53 somatic evolution in peritoneal washes of individuals with BRCA1 germline mutations
Tee, X. R., Hazard, E., Latorre-Esteves, E. S., Kohrn, B. F., Ghezelayagh, T. S., Fredrickson, J., Coombes, C., Radke, M. R., Manhardt, E., Katz, R., et al. (2024) · Gynecologic Oncology · doi:10.1016/j.ygyno.2024.07.690 · Cited by 5
Komarova, N. L., Rignot, C., Fleischman, A. G., & Wodarz, D. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2321525121 · Cited by 5
“These mutants evolve in the hematopoietic system at homeostasis and increase the chances that hematological malignancies as well as other chronic health conditions develop ( 20 ).”
InfluentialMutational landscape of atherosclerotic plaques reveals large clonal cell populations
Steffensen, L. B., Kavan, S., Jensen, P. S., Pedersen, M. K., Bøttger, S. M., Larsen, M. J., Dembić, M., Bergman, O., Matic, L. P., Hedin, U., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.188281 · Cited by 7
“The prevailing understanding is that individuals with CHIP mutations face an increased risk of atherosclerotic cardiovascular disease due to increased leukocyte proinflammatory activity, exacerbating plaque formation (33).”
Clonal dynamics of hematopoietic stem cell compartment in aplastic anemia
Visconte, V., & Maciejewski, J. P. (2022) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.12.003 · Cited by 6
Somatic mutations in VEXAS Syndrome and Erdheim-Chester disease: Inflammatory myeloid diseases
Alcedo, P. E., Gutierrez‐Rodrigues, F., & Patel, B. A. (2022) · Seminars in Hematology · doi:10.1053/j.seminhematol.2022.07.003 · Cited by 5
Toward a systems-level probing of tumor clonality
Grody, E. I., Abraham, A., Shukla, V., & Goyal, Y. (2023) · iScience · doi:10.1016/j.isci.2023.106574 · Cited by 5
“5%, it manifests in 20% of all individuals at age 50, and further increases to 50% by 70 years of age.(96,97) More recent studies using very high-depth sequencing have shown that the incidence of age-associated CHIP could be even higher than previously reported.”
BackgroundKomić, L., Kumrić, M., Urlić, H., Rizikalo, A., Grahovac, M., Komic, J., Tomičić, M., Rušić, D., Kurir, T. T., & Božić, J. (2023) · Life · doi:10.3390/life13061365 · Cited by 9
“Mistakes during DNA polymerase replication are yet another form of mutation [3,6].”
BackgroundInfluentialKruglyak, K. M., O’Kell, A. L., Cohen, T. A., Marshall, M. A., Ruiz-Pérez, C. A., Marass, F., Tynan, J. A., Hicks, S. C., Lytle, K. M., Phelps‐Dunn, A., et al. (2023) · Veterinary Sciences · doi:10.3390/vetsci10070455 · Cited by 5
Loss of Nudt15 thiopurine detoxification increases direct DNA damage in hematopoietic stem cells
Yamashita, N., Kawahara, M., Imai, T., Tatsumi, G., Nishishita-Asai, A., & Andoh, A. (2023) · Scientific Reports · doi:10.1038/s41598-023-38952-7 · Cited by 5
“…defenses against DNA damage upon thiopurine exposure, the number of HSCs significantly decreases after 48 h. DNA damage due to cancer therapies has been reported to initiate clonal hematopoiesis that is related to the development of hematological malignancies and cardiovascular diseases 48,49 .”
Clonal hematopoiesis in frequent whole blood donors
Karpova, D. (2023) · Hematology · doi:10.1182/hematology.2023000483 · Cited by 5
Pourebrahim, R., Montoya, R. H., Akiyama, H., Ostermann, L. B., Khazaei, S., Müftüoğlu, M., Zhao, R., Lesluyes, T., Ayoub, E., Liu, B., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101558 · Cited by 6
“39,40 Aging HSCs are associated with myeloid-biased hematopoiesis, linked to myeloid malignancies like AML.”
Association Between Rheumatoid Arthritis and Clonal Hematopoiesis: A Mendelian Randomization Study
Zhang, J., Zhou, C., & Guan, S. (2024) · Twin Research and Human Genetics · doi:10.1017/thg.2024.24 · Cited by 6
“…of mutated blood cells, including two enzymes involved in DNA methylation (DNMT3A and TET2) and a chromatin regulator (ASXL1) as well as cellular growth signaling (GNAS, GNB1, JAK2, CBL) and the DNA damage response (PPM1D, TP53), are the main drivers mutation of CH (Jaiswal & Ebert, 2019).”
Zhuang, Q., Jin, S., Wang, W., Wang, Y., Tong, H., Liu, Z., & Sun, J. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.10.005 · Cited by 5
Myeloproliferative Neoplasms: The Long Wait for JAK2-Mutant Clone Expansion
Paz, D. L., Ashcroft, P., & Skoda, R. C. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.018 · Cited by 6
Kusne, Y. N., Lasho, T. L., Mangaonkar, A. A., Tefferi, A., Gangat, N., Finke, C. M., Binder, M., Chia, N., & Patnaik, M. M. (2021) · American Journal of Hematology · doi:10.1002/ajh.26297 · Cited by 5
Why Single-Cell Sequencing Has Promise in MDS
Zhang, X., & Grimes, H. L. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.769753 · Cited by 5
“This non-malignant type of clonal outgrowth of hematopoietic cells is referred to as clonal hematopoiesis of indeterminate potential (CHIP) (54, 55).”
BackgroundInfluentialCommon origin and somatic mutation patterns of composite lymphomas and leukemias
Berg, V., Lollies, A., Schneider, M., Johansson, P., Weniger, M. A., Albertini, E., Facchetti, F., Ascani, S., Moawia, A., Bens, S., et al. (2025) · Leukemia · doi:10.1038/s41375-025-02549-y · Cited by 4
“Additionally, mutations in particular genes, such as TET2 , can be found in descendants of clonally expanded HSC/HPC in elderly individuals [16].”
Emerging insights into mosaic errors of immunity
Roosens, W., Demeulemeester, J., Legius, E., Savic, S., & Schrijvers, R. (2025) · Trends in Immunology · doi:10.1016/j.it.2025.09.003 · Cited by 5
Brain somatic mutations in Alzheimer’s disease: linking genetic mosaicism to neurodegeneration
Li, Z., Zhang, J., Liu, Z., Yu, L., Yang, C., Zhang, L., Xiang, Z., Hu, F., Brazh, N., Shu, K., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00895-0 · Cited by 6
Catalano, A., Bonuomo, V., Grano, S., Dhupdale, T. S., Bianchi, A., Dansero, L., Gnavi, R., Sacerdote, C., Fava, C., & Ricceri, F. (2025) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-25-0969 · Cited by 4
Huang, K. K., Hagihara, T., Lian, B. S. X., Ong, Z. X., Lim, S. K., Chong, R. H. H., Srivastava, S., Kang, J. X., Lee, M. Y., Tan, A. L. K., et al. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-0778 · Cited by 4
“Several studies have shown that CH, particularly involving loss-of-function mutations in DNMT3A or TET2 , is linked to a hyperinflammatory state characterized by elevated levels of proinflammatory cytokines such as TNF α , IL6, IL1 β , and IL8 (63–65).”
Clonal independence of CHIP-associated mutations in multiple myeloma
Wobst, J., Wossidlo, N., Truger, M. S., Meggendorfer, M., Kern, W., Haferlach, T., & Haferlach, C. (2026) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2026.2617435 · Cited by 4
“ChiP is rare in individuals under 40 years of age and steadily increases in those >65 years [3].”
Lung cancer in never smokers: from early detection to prevention
Caswell, D. R., Hiley, C. T., Murphy, C., Bao, L. C., & Swanton, C. (2026) · Trends in cancer · doi:10.1016/j.trecan.2025.12.009 · Cited by 5
Kumar, R., Li, L., Urbut, S., Uddin, M. M., Niroula, A., Kanumuri, R., Ramdas, B., Pasupuleti, S. K., Palam, L. R., Wang, X., et al. (2026) · Blood · doi:10.1182/blood.2025032339 · Cited by 4
Clonal Hematopoiesis and Risk of Stroke: Evidence From Over 800 000 Individuals Across 3 Cohorts
Zhao, K., Pershad, Y., Xue, L., Vlasschaert, C., Corty, R. W., Heimlich, J. B., Kooperberg, C. L., Reiner, A. P., & Bick, A. G. (2026) · Stroke · doi:10.1161/strokeaha.125.054128 · Cited by 5
What sets the mutation rate of a cell type in an animal species?
de Manuel, M., Przeworski, M., Spisak, N., & Stolyarova, A. V. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003799 · Cited by 8
“Notably, mutations can increase rates of cell proliferation, leading to clonal expansions that cause signaling problems, compromise tissue function, or lead to cancer [75–78].”
Clonal hematopoiesis of indeterminate potential: a review of its cardiorenal implications and aging
Jalal, A. N., Jhaveri, K. D., & Chowdhury, R. B. (2025) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaf055 · Cited by 5
Nørgaard, M., Rusan, M., Kondrup, K., Sørensen, E. M. G., Weiss, S., Bjerre, M. T., Fredsøe, J., Vang, S., Jensen, J. B., Laere, B. D., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03356-0 · Cited by 4
“The variants in TP53 and SF3B1 were classified as clonal hematopoiesis of indeterminate potential (CHIP) variants, defined as pathogenic variants with a VAF ≥ 2% in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia [45].”
Treatment of Older Patients With ALL
Jabbour, E. J., Haddad, F., & Kantarjian, H. M. (2025) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk-25-473298 · Cited by 4
Xu, P., Zhang, X., Li, D., Jiao, B., Nie, J., Huang, Y., Xia, Z., Li, J., Dan, Y., Huang, X., et al. (2025) · Blood · doi:10.1182/blood.2024027335 · Cited by 5
Lai, J., Xi, Z., Zhu, D., Zhang, Q., Yang, Y., Wang, X., Xia, B., Hou, T., & Feng, H. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000003060 · Cited by 4
“CHIP, while commonly regarded as a precursor state of hematologic neoplasms, it is also associated with dysregulated inflammatory responses and immune system disruptions, which may contribute to the development of a range of diseases, including cancer [ 11 , 28 ] .”
Zhang, J.-L., Tong, S.-L., Zhuang, Q., Jin, S., Li, J., & Sun, J. (2025) · Military Medical Research · doi:10.1186/s40779-025-00654-8 · Cited by 6
“Although CHIP was initially recognized as a precursor state for hematologic malignancies, accumulating evidence implicated it as a systemic risk factor for diverse non-hematologic diseases via immune dysregulation and chronic inflammation [4, 6, 7].”
Clonal Hematopoiesis of Indeterminate Potential After Radiation Therapy
Crants, S., Olson, S., Li, Y., Bejan, C. A., Vlasschaert, C., Mack, T., Pershad, Y., Kishtagari, A., Reed, S. C., Croessmann, S., et al. (2025) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2025.10.006 · Cited by 6
Moyen, T. B., Tomaz, V., Cortês, L. G. F., Rosa, S., Santos, F. P. D. S., Hamerschlak, N., Puga, R., Reis, R. D. S., Petroni, R. C., Silveira, C. N., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-24475-w · Cited by 4
Luijts, T., Elliott, K., Siaw, J. T., de Velde, J. V., Beyls, E., Claeys, A., Lammens, T., Larsson, E., Willaert, W., Vral, A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-14240-8 · Cited by 6
Exploring the intricate cross-talk between clonal expansion and the bone marrow niche
Ngo, S. D., Papazoglou, D., Encabo, H. H., & Bonnet, D. A. (2024) · Frontiers in Hematology · doi:10.3389/frhem.2024.1334807 · Cited by 4
Functional landscape of genome-wide postzygotic somatic mutations between monozygotic twins
Yamamoto, K., Lee, Y., Masuda, T., Ozono, K., Iwatani, Y., Watanabe, M., Okada, Y., & Sakai, N. (2024) · DNA Research · doi:10.1093/dnares/dsae028 · Cited by 4
“35,36 To obtain a more precise estimate of the number of PZMs occurring in this stage, further investigation using other tissues (eg buccal swabs, fibroblasts), additional families, and younger participants will be warranted.”
BackgroundCirculating Tumor DNA in Conjunctival Melanoma: Landscape and Surveillance Value
Tian, H., Shi, H., Chen, J., Zhu, T., Huang, Z., Zong, C., Jia, S., Ruan, J., Ge, S., Yuan, H., et al. (2024) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2024.10.012 · Cited by 4
Clonal hematopoiesis of indeterminate potential (CHIP): A potential contributor to lymphoma
Luo, Q., Zhou, L., Luo, D., & Yu, L. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104589 · Cited by 5
Marshall, C. H., Antonarakis, E. S., & Patnaik, M. M. (2025) · Blood Reviews · doi:10.1016/j.blre.2025.101269 · Cited by 4
Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model
Holmes, S. M., Wells, C. J., Hall, C., McNaughton, A. J. M., Rauh, M. J., & Abraham, S. A. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104747 · Cited by 4
Zhou, K., Gheybi, K., Soh, P. X. Y., & Hayes, V. M. (2025) · Communications Medicine · doi:10.1038/s43856-025-00883-x · Cited by 4
“Our rationale, as human aging increases the frequency of somatic mutations in hematopoietic stem cells, a phenomenon more prevalent in DNA repair genes, while the risk is modest, their rarity has the potential for further misclassi fi cation for germline screening 52 .”
Almotiri, A., Abdelfattah, A., & Rodrigues, N. P. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-1924-7_36 · Cited by 4
Postnatal conservation of human blood- and marrow-specific CD34+ hematopoietic phenotypes
Hammond, C. A., & Eaves, C. J. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.03.004 · Cited by 5
Clinical impact of clonal hematopoiesis on severe COVID- 19 patients without canonical risk factors
Kang, C. K., Choi, B., Kim, S., Sun, C.-H., Yoon, S. H., Kim, K., Chang, E., Jung, J., Choe, P. G., Park, W. B., et al. (2022) · Haematologica · doi:10.3324/haematol.2022.280621 · Cited by 4
Diagnostik bei unklaren Zytopenien – wie und wann suchen wir nach klonaler Hämatopoese?
Haferlach, C., & Heuser, M. (2022) · Die Innere Medizin · doi:10.1007/s00108-022-01402-z · Cited by 6
Clonal heamatopoiesis and associated cardiovascular diseases
Tajiri, K., Suehara, Y., Suzuki, T., & Sekine, I. (2023) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyac210 · Cited by 4
Mitochondrial dynamics as a pathobiological mediator of clonal myeloid disorders
Hayashi, Y., & Harada, H. (2023) · Cancer Science · doi:10.1111/cas.15810 · Cited by 3
Clones of aging: When better fitness can be dangerous
Marongiu, F., Cheri, S., & Laconi, E. (2023) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2023.151340 · Cited by 4
Regulators of clonal hematopoiesis and physiological consequences of this condition
Park, E., Evans, M. A., & Walsh, K. X. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.39 · Cited by 4
“Acknowledging the potential for confusion arising from the phrase, “we will focus on the association between extrinsic and intrinsic stressors and the development CH,” we have refined the sentence to state, “we will on the association between environmental stressors and inherited genetic risk the…”
BackgroundJiang, H., Chen, Z., Wang, P., Li, D., Tao, Y., Hong, X., Jiao, X., Xia, & Zhang, W. (2024) · Cardiovascular Innovations and Applications · doi:10.15212/cvia.2023.0091 · Cited by 4
The potency of hematopoietic stem cell reprogramming for changing immune tone
Daman, A. W., Cheong, J., Berneking, L., & Josefowicz, S. Z. (2024) · Immunological Reviews · doi:10.1111/imr.13335 · Cited by 4
“94 The incidence of CH, associated with a greater risk of hematological malignancies and cardiovascular disease, escalates with age, and its progression is fueled by chronic inflammation.”
BackgroundAge-related decline in LEPR+ hematopoietic stem cell function
Trinh, T. L. P., Ropa, J. P., Cooper, S. H., Aljoufi, A., Sinn, A. L., Capitano, M. L., Broxmeyer, H. E., & Kaplan, M. H. (2023) · Leukemia · doi:10.1038/s41375-023-01815-1 · Cited by 4
“It is well-appreciated that aging is associated with increased incidence of clonal hematopoiesis, leukemic transformation and hematological disorders, and this process starts with the HSC, the cell that gives rise to all other blood and immune cells [13].”
BackgroundSomatic mutations reveal hypermutable brains and are associated with neuropsychiatric disordersPreprint
Bae, T., Fasching, L., Wang, Y., Shin, J. H., Šuvakov, M., Jang, Y., Norton, S., Dias, C., Mariani, J., Jourdon, A., et al. (2022) · medRxiv · doi:10.1101/2022.02.09.22269114 · Cited by 4
Somatic mutations reveal clonal cell populations in atherosclerotic plaquesPreprint
Steffensen, L. B., Kavan, S., Jensen, P., Møller‐Larsen, S., Larsen, M. L., Dembić, M., Andersen, L., Lindholt, J. S., Houlind, K. C., Thomassen, M., et al. (2022) · medRxiv · doi:10.1101/2022.05.16.22275001 · Cited by 4
Editorial: Somatic mutations, genome mosaicism and aging
Lodato, M. A., & Vijg, J. (2023) · Frontiers in Aging · doi:10.3389/fragi.2022.1115408 · Cited by 4
iPSC Models of Leukemia Come of Age
Doulatov, S. R. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0041 · Cited by 4
Lettera, E., Scala, S., Ricci, L. B., Tavella, T., della Volpe, L., Furno, E. L., Kaufmann, K. B., García‐Prat, L., Quaranta, P., Hernández, R. J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.15.557553 · Cited by 4
Tardif, J., Busque, L., Geoffroy, S., Sandoval, J., Perreault, L. L., Mongrain, I., Valois, D., Gaulin, M., Buscarlet, M., Provost, S., et al. (2024) · medRxiv · doi:10.1101/2024.10.17.24315679 · Cited by 6
Mechanism of age-related accumulation of mitochondrial DNA mutations in human bloodPreprint
Gupta, R., Durham, T., Chau, G., Uddin, M. M., Lu, W., Karczewski, K. J., Howrigan, D. P., Natarajan, P., Zhou, W., Neale, B. M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.25.655566 · Cited by 4
“This is consistent with work showing that CH is likely universally present at low fraction 42,43 , which we are now able to detect due to the high depth of mtDNA sequencing.”
Mosaic chromosomal alterations in blood are associated with an increased risk of Alzheimer’s disease
Naito, T., Hirata, K., Jang, B., Lakhani, C. M., Buonfiglioli, A., Lee, W.-P., Valladares, O., Wang, L.-S., Okada, Y., Won, H.-H., et al. (2025) · doi:10.1101/2025.05.29.25328544 · Cited by 4
Therapy-selected clonal hematopoiesis and its role in myeloid neoplasms
Jahn, J., Diamond, B. T., Hsu, J., Montoya, S., Totiger, T. M., Landgren, O., Maura, F., & Taylor, J. (2023) · Leukemia Research · doi:10.1016/j.leukres.2023.107020 · Cited by 3
Fang, J. X., Zou, H.-M., Meng, J., Yu, H., Hu, X., Gu, Q., Wang, S. J., & Liu, X. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100662 · Cited by 3
“This has spawned more research on the involvement of immune cells in the initiation, development, and rupture of atheromatous plaques by mediating inflammation (4, 5).”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
