Abstract
Clonal expansion of hematopoietic cells is first observed in hematological malignancies where all the leukemic cells can be traced back to a single cell carrying oncogenic alterations. Interestingly, expansion of hematopoietic clones with defined genomic alterations, including single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural chromosomal alterations (CAs), is also found in the healthy population. These genomic changes often affect leukemia driver genes. As a result, healthy individuals bearing such clonal hematopoiesis (CH) are at a higher risk of hematological malignancies. In addition to blood cancers, SNV/indel-related CH has been found associated with elevated cardiovascular and all-cause mortality, indicating adverse impacts of abnormalities in the blood on the normal functions of non-hematological tissues. In the past decade, much effort has been invested in understanding the origins of CH and its causal relationship with diseases in hematological and non-hematological tissues. Here, we review recent progress in these areas and discuss future directions that can be pursued to translate the acquired knowledge into better management of CH-related diseases.
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References
Abdelbaset-Ismail A et al (2016) Human haematopoietic stem/progenitor cells express several functional sex hormone receptors. J Cell Mol Med 20:134–146. https://doi.org/10.1111/jcmm.12712
Abdel-Wahab O et al (2012) ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 22:180–193. https://doi.org/10.1016/j.ccr.2012.06.032
Abdel-Wahab O et al (2013) Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med 210:2641–2659. https://doi.org/10.1084/jem.20131141
Abegunde SO, Buckstein R, Wells RA, Rauh MJ (2018) An inflammatory environment containing TNFalpha favors Tet2-mutant clonal hematopoiesis. Exp Hematol 59:60–65. https://doi.org/10.1016/j.exphem.2017.11.002
Abelson S et al (2018) Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 559:400–404. https://doi.org/10.1038/s41586-018-0317-6
Abkowitz JL, Catlin SN, Guttorp P (1996) Evidence that hematopoiesis may be a stochastic process in vivo. Nat Med 2:190–197. https://doi.org/10.1038/nm0296-190
Agathocleous M et al (2017) Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature 549:476–481. https://doi.org/10.1038/nature23876
Arends CM et al (2018) Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. Leukemia 32:1908–1919. https://doi.org/10.1038/s41375-018-0047-7
Asada S et al (2018) Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nat Commun 9:2733. https://doi.org/10.1038/s41467-018-05085-9
Ashcroft P, Manz MG, Bonhoeffer S (2017) Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments. PLoS Comput Biol 13:e1005803. https://doi.org/10.1371/journal.pcbi.1005803
Avagyan S et al (2021) Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science 374:768–772. https://doi.org/10.1126/science.aba9304
Balasubramani A et al (2015) Cancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1–BAP1 complex. Nat Commun 6:7307. https://doi.org/10.1038/ncomms8307
Bennett BD et al (1996) A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 6:1170–1180. https://doi.org/10.1016/s0960-9822(02)70684-2
Bick AG et al (2020) Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 586:763–768. https://doi.org/10.1038/s41586-020-2819-2
Buscarlet M et al (2018) Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A. Blood 132:277–280. https://doi.org/10.1182/blood-2018-01-829937
Busch K et al (2015) Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature 518:542–546. https://doi.org/10.1038/nature14242
Busque L et al (2012) Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet 44:1179–1181. https://doi.org/10.1038/ng.2413
Cai Z et al (2018) Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis. Cell Stem Cell 23:833–849. https://doi.org/10.1016/j.stem.2018.10.013
Cara et al (2015) Mutant U2AF1 expression alters hematopoiesis and Pre-mRNA splicing in vivo. Cancer Cell 27:631–643. https://doi.org/10.1016/j.ccell.2015.04.008
Carty SA et al (2018) The loss of TET2 promotes CD8+ T cell memory differentiation. J Immunol 200:82–91. https://doi.org/10.4049/jimmunol.1700559
Case LK et al (2013) The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease. Genome Res 23:1474–1485. https://doi.org/10.1101/gr.156703.113
Challen GA et al (2012) Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet 44:23–31. https://doi.org/10.1038/ng.1009
Chen S et al (2019) Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway. Nat Commun 10:5649. https://doi.org/10.1038/s41467-019-13542-2
Cimmino L et al (2017) Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell 170:1079–1095. https://doi.org/10.1016/j.cell.2017.07.032
Cull AH, Snetsinger B, Buckstein R, Wells RA, Rauh MJ (2017) Tet2 restrains inflammatory gene expression in macrophages. Exp Hematol 55:56–70. https://doi.org/10.1016/j.exphem.2017.08.001
Desai P et al (2018) Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat Med 24:1015–1023. https://doi.org/10.1038/s41591-018-0081-z
Dumanski JP et al (2021) Immune cells lacking Y chromosome show dysregulation of autosomal gene expression. Cell Mol Life Sci 78:4019–4033. https://doi.org/10.1007/s00018-021-03822-w
Fey M et al (1994) Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe. Blood 83:931–938. https://doi.org/10.1182/blood.v83.4.931.931
Fialkow PJ (1973) Primordial cell pool size and lineage relationships of five human cell types. Ann Hum Genet 37:39–48. https://doi.org/10.1111/j.1469-1809.1973.tb01813.x
Fialkow PJ, Gartler SM, Yoshida A (1967) Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci U S A 58:1468–1471. https://doi.org/10.1073/pnas.58.4.1468
Forsberg LA et al (2014) Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat Genet 46:624–628. https://doi.org/10.1038/ng.2966
Fujino T et al (2021) Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway. Nat Commun 12:1826. https://doi.org/10.1038/s41467-021-22053-y
Fuster JJ et al (2017) Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355:842–847. https://doi.org/10.1126/science.aag1381
Fuster JJ et al (2020) TET2-loss-of-function-driven clonal hematopoiesis exacerbates experimental insulin resistance in aging and obesity. Cell Rep 33:108326. https://doi.org/10.1016/j.celrep.2020.108326
Gale RE, Wheadon H, Linch DC (1991) X-chromosome inactivation patterns using HPRT and PGK polymorphisms in haematologically normal and post-chemotherapy females. Br J Haematol 79:193–197. https://doi.org/10.1111/j.1365-2141.1991.tb04521.x
Gamper CJ, Agoston AT, Nelson WG, Powell JD (2009) Identification of DNA methyltransferase 3a as a T cell receptor-induced regulator of Th1 and Th2 differentiation. J Immunol 183:2267–2276. https://doi.org/10.4049/jimmunol.0802960
Gao T et al (2021) Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis. Nat Commun 12:338. https://doi.org/10.1038/s41467-020-20565-7
Genovese G et al (2014) Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371:2477–2487. https://doi.org/10.1056/nejmoa1409405
Haitjema S et al (2017) Loss of Y chromosome in blood is associated with major cardiovascular events during follow-up in men after carotid endarterectomy. Circ Cardiovasc Genet 10:e001544. https://doi.org/10.1161/circgenetics.116.001544
Herens C, Brasseur E, Jamar M, Vierset L, Schoenen I, Koulischer L (1992) Loss of the Y chromosome from normal and neoplastic bone marrows. Genes Chromosom Cancer 5:83–88. https://doi.org/10.1002/gcc.2870050112
Hormaechea-Agulla D et al (2021) Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling. Cell Stem Cell 28:1428–1442. https://doi.org/10.1016/j.stem.2021.03.002
Hsiue EH et al (2021) Targeting a neoantigen derived from a common TP53 mutation. Science 371:8697. https://doi.org/10.1126/science.abc8697
Hsu YC et al (2017) The distinct biological implications of Asxl1 mutation and its roles in leukemogenesis revealed by a knock-in mouse model. J Hematol Oncol 10:139. https://doi.org/10.1186/s13045-017-0508-x
Hsu JI et al (2018) PPM1D mutations drive clonal hematopoiesis in response to cytotoxic chemotherapy. Cell Stem Cell 23:700–713. https://doi.org/10.1016/j.stem.2018.10.004
Ichiyama K et al (2015) The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells. Immunity 42:613–626. https://doi.org/10.1016/j.immuni.2015.03.005
Inoue D et al (2013) Myelodysplastic syndromes are induced by histone methylation “altering ASXL1 mutations”. J Clin Investig 123:4627–4640. https://doi.org/10.1172/jci70739
Inoue D et al (2018) A novel ASXL1-OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies. Leukemia 32:1327–1337. https://doi.org/10.1038/s41375-018-0083-3
Jacobs KB et al (2012) Detectable clonal mosaicism and its relationship to aging and cancer. Nat Genet 44:651–658. https://doi.org/10.1038/ng.2270
Jaiswal S et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371:2488–2498. https://doi.org/10.1056/nejmoa1408617
Jaiswal S et al (2017) Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med 377:111–121. https://doi.org/10.1056/nejmoa1701719
Jones AV et al (2009) JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet 41:446–449. https://doi.org/10.1038/ng.334
Kahn JD et al (2018) PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells. Blood 132:1095–1105. https://doi.org/10.1182/blood-2018-05-850339
Kilpivaara O et al (2009) A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet 41:455–459. https://doi.org/10.1038/ng.342
Kim E et al (2015) SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition. Cancer Cell 27:617–630. https://doi.org/10.1016/j.ccell.2015.04.006
Kleppe M et al (2015) JAK–STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response. Cancer Discov 5:316–331. https://doi.org/10.1158/2159-8290.cd-14-0736
Koh KP et al (2011) Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8:200–213. https://doi.org/10.1016/j.stem.2011.01.008
Kondo M et al (2003) Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 21:759–806. https://doi.org/10.1146/annurev.immunol.21.120601.141007
Kunimoto H et al (2014) Tet2-mutated myeloid progenitors possess aberrant in vitro self-renewal capacity. Blood 123:2897–2899. https://doi.org/10.1182/blood-2014-01-552471
Ladle BH et al (2016) De novo DNA methylation by DNA methyltransferase 3a controls early effector CD8+ T-cell fate decisions following activation. Proc Natl Acad Sci U S A 113:10631–10636. https://doi.org/10.1073/pnas.1524490113
Laurie CC et al (2012) Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet 44:642–650. https://doi.org/10.1038/ng.2271
Lee SC-W et al (2018) Synthetic lethal and convergent biological effects of cancer-associated spliceosomal gene mutations. Cancer Cell 34:225–241. https://doi.org/10.1016/j.ccell.2018.07.003
Lee-Six H et al (2018) Population dynamics of normal human blood inferred from somatic mutations. Nature 561:473–478. https://doi.org/10.1038/s41586-018-0497-0
Leoni C et al (2017) Dnmt3a restrains mast cell inflammatory responses. Proc Natl Acad Sci U S A 114:E1490–E1499. https://doi.org/10.1073/pnas.1616420114
Li Z et al (2011) Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 118:4509–4518. https://doi.org/10.1182/blood-2010-12-325241
Liao M et al (2022) Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis. Acta Pharm Sin B 12:678–691. https://doi.org/10.1016/j.apsb.2021.09.015
Liu X, Gong Y (2019) Isocitrate dehydrogenase inhibitors in acute myeloid leukemia. Biomarker Res 7:22. https://doi.org/10.1186/s40364-019-0173-z
Ljungström V et al (2022) Loss of Y and clonal hematopoiesis in blood—two sides of the same coin? Leukemia 36:889–891. https://doi.org/10.1038/s41375-021-01456-2
Loftfield E et al (2018) Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank. Sci Rep 8:12316. https://doi.org/10.1038/s41598-018-30759-1
Loh P-R et al (2018) Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 559:350–355. https://doi.org/10.1038/s41586-018-0321-x
Loh P-R, Genovese G, McCarroll SA (2020) Monogenic and polygenic inheritance become instruments for clonal selection. Nature 584:136–141. https://doi.org/10.1038/s41586-020-2430-6
Lopez-Moyado IF et al (2019) Paradoxical association of TET loss of function with genome-wide DNA hypomethylation. Proc Natl Acad Sci U S A 116:16933–16942. https://doi.org/10.1073/pnas.1903059116
Madzo J et al (2014) Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep 6:231–244. https://doi.org/10.1016/j.celrep.2013.11.044
Malcovati L et al (2017) Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 129:3371–3378. https://doi.org/10.1182/blood-2017-01-763425
Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J (2010) Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol 8:e1000324. https://doi.org/10.1371/journal.pbio.1000324
Matatall KA et al (2016) Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation. Cell Rep 17:2584–2595. https://doi.org/10.1016/j.celrep.2016.11.031
McKerrell T et al (2015) Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep 10:1239–1245. https://doi.org/10.1016/j.celrep.2015.02.005
Meisel M et al (2018) Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557:580–584. https://doi.org/10.1038/s41586-018-0125-z
Miller PG et al (2022) Association of clonal hematopoiesis with chronic obstructive pulmonary disease. Blood 139:357–368. https://doi.org/10.1182/blood.2021013531
Moran-Crusio K et al (2011) Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20:11–24. https://doi.org/10.1016/j.ccr.2011.06.001
Nagase R et al (2018) Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation. J Exp Med 215:1729–1747. https://doi.org/10.1084/jem.20171151
Niroula A et al (2021) Distinction of lymphoid and myeloid clonal hematopoiesis. Nat Med 27:1921–1927. https://doi.org/10.1038/s41591-021-01521-4
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b Are essential for de novo methylation and mammalian development. Cell 99:247–257. https://doi.org/10.1016/S0092-8674(00)81656-6
Olcaydu D et al (2009) A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet 41:450–454. https://doi.org/10.1038/ng.341
Osorio FG et al (2018) Somatic mutations reveal lineage relationships and age-related mutagenesis in human hematopoiesis. Cell Rep 25:2308–2316. https://doi.org/10.1016/j.celrep.2018.11.014
Ostrander EL et al (2020) Divergent effects of Dnmt3a and Tet2 mutations on hematopoietic progenitor cell fitness. Stem Cell Rep 14:551–560. https://doi.org/10.1016/j.stemcr.2020.02.011
Pei W et al (2017) Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature 548:456–460. https://doi.org/10.1038/nature23653
Pierre RV, Hoagland HC (1972) Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. Cancer 30:889–894. https://doi.org/10.1002/1097-0142(197210)30:4<889::aid-cncr2820300405>3.0.co;2-1
Pietras EM et al (2016) Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat Cell Biol 18:607–618. https://doi.org/10.1038/ncb3346
Pollyea DA et al (2019) Myelodysplastic syndrome-associated spliceosome gene mutations enhance innate immune signaling. Haematologica 104:e388–e392. https://doi.org/10.3324/haematol.2018.214155
Rasmussen KD et al (2015) Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev 29:910–922. https://doi.org/10.1101/gad.260174.115
Saiki R et al (2021) Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis. Nat Med 27:1239–1249. https://doi.org/10.1038/s41591-021-01411-9
Sano S et al (2018a) CRISPR-mediated gene editing to assess the roles of Tet2 and Dnmt3a in clonal hematopoiesis and cardiovascular disease. Circ Res 123:335–341. https://doi.org/10.1161/circresaha.118.313225
Sano S et al (2018b) Tet2-Mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1beta/NLRP3 inflammasome. J Am Coll Cardiol 71:875–886. https://doi.org/10.1016/j.jacc.2017.12.037
Sano S et al (2019) JAK2 (V617F)-mediated clonal hematopoiesis accelerates pathological remodeling in murine heart failure. JACC Basic Transl Sci 4:684–697. https://doi.org/10.1016/j.jacbts.2019.05.013
Seiler M et al (2018) H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat Med 24:497–504. https://doi.org/10.1038/nm.4493
Smith MA et al (2019) U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nat Cell Biol 21:640–650. https://doi.org/10.1038/s41556-019-0314-5
Steensma DP et al (2015) Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 126:9–16. https://doi.org/10.1182/blood-2015-03-631747
Sun J et al (2014) Clonal dynamics of native haematopoiesis. Nature 514:322–327. https://doi.org/10.1038/nature13824
Terao C et al (2019) GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation. Nat Commun 10:4719. https://doi.org/10.1038/s41467-019-12705-5
Terao C et al (2020) Chromosomal alterations among age-related haematopoietic clones in Japan. Nature 584:130–135. https://doi.org/10.1038/s41586-020-2426-2
Thomas RM, Gamper CJ, Ladle BH, Powell JD, Wells AD (2012) De novo DNA methylation is required to restrict T helper lineage plasticity. J Biol Chem 287:22900–22909. https://doi.org/10.1074/jbc.m111.312785
Thompson DJ et al (2019) Genetic predisposition to mosaic Y chromosome loss in blood. Nature 575:652–657. https://doi.org/10.1038/s41586-019-1765-3
Uni M et al (2019) Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification. Leukemia 33:191–204. https://doi.org/10.1038/s41375-018-0198-6
Velten L et al (2021) Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics. Nat Commun 12:1366. https://doi.org/10.1038/s41467-021-21650-1
Watson CJ, Blundell JR (2022) Mutation rates and fitness consequences of mosaic chromosomal alterations in blood. bioRxiv. https://doi.org/10.1101/2022.05.07.491016
Watson CJ et al (2020) The evolutionary dynamics and fitness landscape of clonal hematopoiesis. Science 367:1449–1454. https://doi.org/10.1126/science.aay9333
Welch JS et al (2012) The origin and evolution of mutations in acute myeloid leukemia. Cell 150:264–278. https://doi.org/10.1016/j.cell.2012.06.023
Williams N et al (2022) Life histories of myeloproliferative neoplasms inferred from phylogenies. Nature 602:162–168. https://doi.org/10.1038/s41586-021-04312-6
Wong TN et al (2018) Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential. Nat Commun 9:455. https://doi.org/10.1038/s41467-018-02858-0
Wright DJ et al (2017) Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility. Nat Genet 49:674–679. https://doi.org/10.1038/ng.3821
Xie M et al (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 20:1472–1478. https://doi.org/10.1038/nm.3733
Yamamoto K et al (2021) A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells. Cell Rep 36:109576. https://doi.org/10.1016/j.celrep.2021.109576
Yamashita M, Passegue E (2019) TNF-alpha coordinates hematopoietic stem cell survival and myeloid regeneration. Cell Stem Cell 25:357–372. https://doi.org/10.1016/j.stem.2019.05.019
Young AL, Challen GA, Birmann BM, Druley TE (2016) Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nat Commun 7:12484. https://doi.org/10.1038/ncomms12484
Yura Y et al (2021) The cancer therapy-related clonal hematopoiesis driver gene Ppm1d promotes inflammation and non-ischemic heart failure in mice. Circ Res 129:684–698. https://doi.org/10.1161/circresaha.121.319314
Zekavat SM et al (2021) Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. Nat Med 27:1012–1024. https://doi.org/10.1038/s41591-021-01371-0
Zhang Q et al (2015) Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525:389–393. https://doi.org/10.1038/nature15252
Zhang X et al (2016) DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells. Nat Genet 48:1014–1023. https://doi.org/10.1038/ng.3610
Zhang Q et al (2022a) Mosaic loss of chromosome Y promotes leukemogenesis and clonal hematopoiesis. JCI Insight 7:e153768. https://doi.org/10.1172/jci.insight.153768
Zhang S et al (2022b) Advanced strategies for therapeutic targeting of wild-type and mutant p53 in cancer. Biomolecules 12:548. https://doi.org/10.3390/biom12040548
Zhou W et al (2016) Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat Genet 48:563–568. https://doi.org/10.1038/ng.3545
Zhu F et al (2019) The GABA receptor GABRR1 is expressed on and functional in hematopoietic stem cells and megakaryocyte progenitors. Proc Natl Acad Sci U S A 116:18416–18422. https://doi.org/10.1073/pnas.1906251116
Zink F et al (2017) Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 130:742–752. https://doi.org/10.1182/blood-2017-02-769869
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Zhang, Z., Sun, J. (2023). The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases. In: Zhao, M., Qian, P. (eds) Hematopoietic Stem Cells. Advances in Experimental Medicine and Biology, vol 1442. Springer, Singapore. https://doi.org/10.1007/978-981-99-7471-9_5
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