1932

Abstract

Clonal hematopoiesis (CH) is an age-related process whereby hematopoietic stem and progenitor cells (HSPCs) acquire mutations that lead to a proliferative advantage and clonal expansion. The most commonly mutated genes are epigenetic regulators, DNA damage response genes, and splicing factors, which are essential to maintain functional HSPCs and are frequently involved in the development of hematologic malignancies. Established risk factors for CH, including age, prior cytotoxic therapy, and smoking, increase the risk of acquiring CH and/or may increase CH fitness. CH has emerged as a novel risk factor in many age-related diseases, such as hematologic malignancies, cardiovascular disease, diabetes, and autoimmune disorders, among others. Future characterization of the mechanisms driving CH evolution will be critical to develop preventative and therapeutic approaches.

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2024-08-27
2024-09-09
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Literature Cited

  1. 1.
    Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, et al. 2018.. Prediction of acute myeloid leukaemia risk in healthy individuals. . Nature 559::4004
    [Crossref] [Google Scholar]
  2. 2.
    Abplanalp WT, Mas-Peiro S, Cremer S, John D, Dimmeler S, Zeiher AM. 2020.. Association of clonal hematopoiesis of indeterminate potential with inflammatory gene expression in patients with severe degenerative aortic valve stenosis or chronic postischemic heart failure. . JAMA Cardiol. 5::117075
    [Crossref] [Google Scholar]
  3. 3.
    Acuna-Hidalgo R, Sengul H, Steehouwer M, van de Vorst M, Vermeulen SH, et al. 2017.. Ultra-sensitive sequencing identifies high prevalence of clonal hematopoiesis-associated mutations throughout adult life. . Am. J. Hum. Genet. 101::5064
    [Crossref] [Google Scholar]
  4. 4.
    Adesoye T, Katz MHG, Offodile AC II. 2023.. Meeting trial participants where they are: decentralized clinical trials as a patient-centered paradigm for enhancing accrual and diversity in surgical and multidisciplinary trials in oncology. . JCO Oncol. Pract. 19::31721
    [Crossref] [Google Scholar]
  5. 5.
    Agrawal M, Niroula A, Cunin P, McConkey M, Shkolnik V, et al. 2022.. TET2-mutant clonal hematopoiesis and risk of gout. . Blood 140::1094103
    [Crossref] [Google Scholar]
  6. 6.
    Al-Rifai R, Vandestienne M, Lavillegrand J-R, Mirault T, Cornebise J, et al. 2022.. JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm. . Nat. Commun. 13::6592
    [Crossref] [Google Scholar]
  7. 7.
    Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, et al. 2022.. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. . Blood 140::120028
    [Crossref] [Google Scholar]
  8. 8.
    Arends CM, Liman TG, Strzelecka PM, Kufner A, Löwe P, et al. 2023.. Associations of clonal hematopoiesis with recurrent vascular events and death in patients with incident ischemic stroke. . Blood 141::78799
    [Crossref] [Google Scholar]
  9. 9.
    Arends CM, Weiss M, Christen F, Eulenberg-Gustavus C, Rousselle A, et al. 2020.. Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. . Haematologica 105::e26467
    [Crossref] [Google Scholar]
  10. 10.
    Assmus B, Cremer S, Kirschbaum K, Culmann D, Kiefer K, et al. 2020.. Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations. . Eur. Heart J. 42::25765
    [Crossref] [Google Scholar]
  11. 11.
    Batalini F, Peacock EG, Stobie L, Robertson A, Garber J, et al. 2019.. Li-Fraumeni syndrome: not a straightforward diagnosis anymore—the interpretation of pathogenic variants of low allele frequency and the differences between germline PVs, mosaicism, and clonal hematopoiesis. . Breast Cancer Res. 21::107
    [Crossref] [Google Scholar]
  12. 12.
    Bhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, et al. 2022.. Clonal hematopoiesis is associated with higher risk of stroke. . Stroke 53::78897
    [Crossref] [Google Scholar]
  13. 13.
    Bick AG, Pirruccello JP, Griffin GK, Gupta N, Gabriel S, et al. 2019.. Genetic interleukin 6 signaling deficiency attenuates cardiovascular risk in clonal hematopoiesis. . Circulation 141::12431
    [Crossref] [Google Scholar]
  14. 14.
    Bick AG, Weinstock JS, Nandakumar SK, Fulco CP, Bao EL, et al. 2020.. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. . Nature 586::76368
    [Crossref] [Google Scholar]
  15. 15.
    Blokzijl F, de Ligt J, Jager M, Sasselli V, Roerink S, et al. 2016.. Tissue-specific mutation accumulation in human adult stem cells during life. . Nature 538::26064
    [Crossref] [Google Scholar]
  16. 16.
    Böhme M, Desch S, Rosolowski M, Scholz M, Krohn K, et al. 2022.. Impact of clonal hematopoiesis in patients with cardiogenic shock complicating acute myocardial infarction. . J. Am. Coll. Cardiol. 80::154556
    [Crossref] [Google Scholar]
  17. 17.
    Bolton KL, Gillis NK, Coombs CC, Takahashi K, Zehir A, et al. 2019.. Managing clonal hematopoiesis in patients with solid tumors. . J. Clin. Oncol. 37::711
    [Crossref] [Google Scholar]
  18. 18.
    Bolton KL, Koh Y, Foote MB, Im H, Jee J, et al. 2021.. Clonal hematopoiesis is associated with risk of severe Covid-19. . Nat. Commun. 12::5975
    [Crossref] [Google Scholar]
  19. 19.
    Bolton KL, Ptashkin RN, Gao T, Braunstein L, Devlin SM, et al. 2020.. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. . Nat. Genet. 52::121926
    [Crossref] [Google Scholar]
  20. 20.
    Bouzid H, Belk JA, Jan M, Qi Y, Sarnowski C, et al. 2023.. Clonal hematopoiesis is associated with protection from Alzheimer's disease. . Nat. Med. 29::166270
    [Crossref] [Google Scholar]
  21. 21.
    Buscarlet M, Provost S, Zada YF, Barhdadi A, Bourgoin V, et al. 2017.. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. . Blood 130::75362
    [Crossref] [Google Scholar]
  22. 22.
    Buscarlet M, Provost S, Zada YF, Bourgoin V, Mollica L, et al. 2018.. Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A. . Blood 132::27780
    [Crossref] [Google Scholar]
  23. 23.
    Busque L, Mio R, Mattioli J, Brais E, Blais N, et al. 1996.. Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. . Blood 88::5965
    [Crossref] [Google Scholar]
  24. 24.
    Busque L, Patel JP, Figueroa M, Vasanthakumar A, Provost S, et al. 2012.. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. . Nat. Genet. 44::117981
    [Crossref] [Google Scholar]
  25. 25.
    Challen GA, Sun D, Jeong M, Luo M, Jelinek J, et al. 2011.. Dnmt3a is essential for hematopoietic stem cell differentiation. . Nat. Genet. 44::2331
    [Crossref] [Google Scholar]
  26. 26.
    Chin DWL, Yoshizato T, Virding Culleton S, Grasso F, Barbachowska M, et al. 2022.. Aged healthy mice acquire clonal hematopoiesis mutations. . Blood 139::62934
    [Crossref] [Google Scholar]
  27. 27.
    Choi EJ, Cho YU, Hur EH, Park HS, Choi Y, et al. 2022.. Clinical implications and genetic features of clonal cytopenia of undetermined significance compared to lower-risk myelodysplastic syndrome. . Br. J. Haematol. 198::70312
    [Crossref] [Google Scholar]
  28. 28.
    Cochran JD, Yura Y, Thel MC, Doviak H, Polizio AH, et al. 2023.. Clonal hematopoiesis in clinical and experimental heart failure with preserved ejection fraction. . Circulation 148::116578
    [Crossref] [Google Scholar]
  29. 29.
    Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, et al. 2017.. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. . Cell Stem Cell 21::37482.e4
    [Crossref] [Google Scholar]
  30. 30.
    Copley MR, Beer PA, Eaves CJ. 2012.. Hematopoietic stem cell heterogeneity takes center stage. . Cell Stem Cell 10::69097
    [Crossref] [Google Scholar]
  31. 31.
    D'Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, et al. 2008.. General cardiovascular risk profile for use in primary care. . Circulation 117::74353
    [Crossref] [Google Scholar]
  32. 32.
    Dawoud AAZ, Tapper WJ, Cross NCP. 2023.. Age-related loss of chromosome Y is associated with levels of sex hormone binding globulin and clonal hematopoiesis defined by TET2, TP53, and CBL mutations. . Sci. Adv. 9::eade9746
    [Crossref] [Google Scholar]
  33. 33.
    Desai P, Mencia-Trinchant N, Savenkov O, Simon MS, Cheang G, et al. 2018.. Somatic mutations precede acute myeloid leukemia years before diagnosis. . Nat. Med. 24::101523
    [Crossref] [Google Scholar]
  34. 34.
    Dumanski JP, Lambert J-C, Rasi C, Giedraitis V, Davies H, et al. 2016.. Mosaic loss of chromosome Y in blood is associated with Alzheimer disease. . Am. J. Hum. Genet. 98::120819
    [Crossref] [Google Scholar]
  35. 35.
    Dumanski JP, Rasi C, Lönn M, Davies H, Ingelsson M, et al. 2015.. Smoking is associated with mosaic loss of chromosome Y. . Science 347::8183
    [Crossref] [Google Scholar]
  36. 36.
    Duncavage EJ, Jacoby MA, Chang GS, Miller CA, Edwin N, et al. 2018.. Mutation clearance after transplantation for myelodysplastic syndrome. . N. Engl. J. Med. 379::102841
    [Crossref] [Google Scholar]
  37. 37.
    Dzierzak E, Speck NA. 2008.. Of lineage and legacy: the development of mammalian hematopoietic stem cells. . Nat. Immunol. 9::12936
    [Crossref] [Google Scholar]
  38. 38.
    Elias HK, Bryder D, Park CY. 2017.. Molecular mechanisms underlying lineage bias in aging hematopoiesis. . Semin. Hematol. 54::411
    [Crossref] [Google Scholar]
  39. 39.
    Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, et al. 2005.. The origins of age-related proinflammatory state. . Blood 105::229499
    [Crossref] [Google Scholar]
  40. 40.
    Fialkow PJ, Gartler SM, Yoshida A. 1967.. Clonal origin of chronic myelocytic leukemia in man. . PNAS 58::146871
    [Crossref] [Google Scholar]
  41. 41.
    Fidler TP, Xue C, Yalcinkaya M, Hardaway B, Abramowicz S, et al. 2021.. The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. . Nature 592::296301
    [Crossref] [Google Scholar]
  42. 42.
    Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA, et al. 2018.. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. . Nature 558::30712
    [Crossref] [Google Scholar]
  43. 43.
    Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, et al. 2017.. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. . Science 355::84247
    [Crossref] [Google Scholar]
  44. 44.
    Gallì A, Todisco G, Catamo E, Sala C, Elena C, et al. 2021.. Relationship between clone metrics and clinical outcome in clonal cytopenia. . Blood 138::96576
    [Crossref] [Google Scholar]
  45. 45.
    Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, et al. 2014.. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. . N. Engl. J. Med. 371::247787
    [Crossref] [Google Scholar]
  46. 46.
    Gibson CJ, Kim HT, Zhao L, Murdock HM, Hambley B, et al. 2022.. Donor clonal hematopoiesis and recipient outcomes after transplantation. . J. Clin. Oncol. 40::189201
    [Crossref] [Google Scholar]
  47. 47.
    Gibson CJ, Lindsley RC, Tchekmedyian V, Mar BG, Shi J, et al. 2017.. Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma. . J. Clin. Oncol. 35::1598605
    [Crossref] [Google Scholar]
  48. 48.
    Gillis NK, Ball M, Zhang Q, Ma Z, Zhao Y, et al. 2017.. Clonal haemopoiesis and therapy-related myeloid malignancies in elderly patients: a proof-of-concept, case-control study. . Lancet Oncol. 18::11221
    [Crossref] [Google Scholar]
  49. 49.
    Grassmann F, Kiel C, den Hollander AI, Weeks DE, Lotery A, et al. 2019.. Y chromosome mosaicism is associated with age-related macular degeneration. . Eur. J. Hum. Genet. 27::3641
    [Crossref] [Google Scholar]
  50. 50.
    Gumuser ED, Schuermans A, Cho SMJ, Sporn ZA, Uddin MM, et al. 2023.. Clonal hematopoiesis of indeterminate potential predicts adverse outcomes in patients with atherosclerotic cardiovascular disease. . J. Am. Coll. Cardiol. 81::19962009
    [Crossref] [Google Scholar]
  51. 51.
    Haitjema S, Kofink D, van Setten J, van der Laan SW, Schoneveld AH, 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
    [Crossref] [Google Scholar]
  52. 52.
    Haring B, Reiner AP, Liu J, Tobias DK, Whitsel E, et al. 2021.. Healthy lifestyle and clonal hematopoiesis of indeterminate potential: results from the Women's Health Initiative. . J. Am. Heart Assoc. 10::e018789
    [Crossref] [Google Scholar]
  53. 53.
    Hirata T, Hishimoto A, Otsuka I, Okazaki S, Boku S, et al. 2018.. Investigation of chromosome Y loss in men with schizophrenia. . Neuropsychiatr. Dis. Treat. 14::211522
    [Crossref] [Google Scholar]
  54. 54.
    Honigberg MC, Zekavat SM, Niroula A, Griffin GK, Bick AG, et al. 2020.. Premature menopause, clonal hematopoiesis, and coronary artery disease in postmenopausal women. . Circulation 143::41023
    [Crossref] [Google Scholar]
  55. 55.
    Horn LV, Carson JAS, Appel LJ, Burke LE, Economos C, et al. 2016.. Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines: a scientific statement from the American Heart Association. . Circulation 134::e50529
    [Google Scholar]
  56. 56.
    Hsu JI, Dayaram T, Tovy A, De Braekeleer E, Jeong M, et al. 2018.. PPM1D mutations drive clonal hematopoiesis in response to cytotoxic chemotherapy. . Cell Stem Cell 23::70013.e6
    [Crossref] [Google Scholar]
  57. 57.
    Husby S, Favero F, Nielsen C, Sørensen BS, Bæch J, et al. 2020.. Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study. . Leukemia 34::325668
    [Crossref] [Google Scholar]
  58. 58.
    Jaiswal S. 2020.. Clonal hematopoiesis and nonhematologic disorders. . Blood 136::160614
    [Google Scholar]
  59. 59.
    Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, et al. 2014.. Age-related clonal hematopoiesis associated with adverse outcomes. . N. Engl. J. Med. 371::248898
    [Crossref] [Google Scholar]
  60. 60.
    Jaiswal S, Libby P. 2020.. Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease. . Nat. Rev. Cardiol. 17::13744
    [Crossref] [Google Scholar]
  61. 61.
    Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, et al. 2017.. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. . N. Engl. J. Med. 377::11121
    [Crossref] [Google Scholar]
  62. 62.
    Jakubek YA, Reiner AP, Honigberg MC. 2023.. Risk factors for clonal hematopoiesis of indeterminate potential and mosaic chromosomal alterations. . Transl. Res. 255::17180
    [Crossref] [Google Scholar]
  63. 63.
    Kanate AS, Majhail NS, Savani BN, Bredeson C, Champlin RE, et al. 2020.. Indications for hematopoietic cell transplantation and immune effector cell therapy: guidelines from the American Society for Transplantation and Cellular Therapy. . Biol. Blood Marrow Transplant. 26::124756
    [Crossref] [Google Scholar]
  64. 64.
    Kar SP, Quiros PM, Gu M, Jiang T, Mitchell J, et al. 2022.. Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis. . Nat. Genet. 54::115566
    [Crossref] [Google Scholar]
  65. 65.
    Khot UN, Khot MB, Topol EJ. 2004.. Traditional risk factors for coronary heart disease—reply. . JAMA 291::299
    [Google Scholar]
  66. 66.
    Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, et al. 2022.. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. . Leukemia 36::170319
    [Crossref] [Google Scholar]
  67. 67.
    Kim KH, Kim T, Novitzky-Basso I, Lee H, Yoo Y, et al. 2023.. Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up. . Haematologica 108::181726
    [Crossref] [Google Scholar]
  68. 68.
    Kim PG, Niroula A, Shkolnik V, McConkey M, Lin AE, et al. 2021.. Dnmt3a-mutated clonal hematopoiesis promotes osteoporosis. . J. Exp. Med. 218::e20211872
    [Crossref] [Google Scholar]
  69. 69.
    Laurenti E, Göttgens B. 2018.. From haematopoietic stem cells to complex differentiation landscapes. . Nature 553::41826
    [Crossref] [Google Scholar]
  70. 70.
    Lee S, Hsu J, Tahri Y, Chen Z, Shore TB, et al. 2018.. Does presence of persistent molecular mutations matter in AML patients undergoing allogeneic stem cell transplant?. Blood 132:(Suppl. 1):2172
    [Crossref] [Google Scholar]
  71. 71.
    Levin MG, Nakao T, Zekavat SM, Koyama S, Bick AG, et al. 2022.. Genetics of smoking and risk of clonal hematopoiesis. . Sci. Rep. 12::7248
    [Crossref] [Google Scholar]
  72. 72.
    Li M, Binder M, Lasho T, Ferrer A, Gangat N, et al. 2021.. Clinical, molecular, and prognostic comparisons between CCUS and lower-risk MDS: a study of 187 molecularly annotated patients. . Blood Adv. 5::227278
    [Crossref] [Google Scholar]
  73. 73.
    Libby P, Nahrendorf M, Swirski FK. 2016.. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum. .” J. Am. Coll. Cardiol. 67::1091103
    [Crossref] [Google Scholar]
  74. 74.
    Lleo A, Oertelt-Prigione S, Bianchi I, Caliari L, Finelli P, et al. 2013.. Y chromosome loss in male patients with primary biliary cirrhosis. . J. Autoimmun. 41::8791
    [Crossref] [Google Scholar]
  75. 75.
    Loftfield E, Zhou W, Graubard BI, Yeager M, Chanock SJ, et al. 2018.. Predictors of mosaic chromosome Y loss and associations with mortality in the UK Biobank. . Sci. Rep. 8::12316
    [Crossref] [Google Scholar]
  76. 76.
    Malcovati L, Gallì A, Travaglino E, Ambaglio I, Rizzo E, et al. 2017.. Clinical significance of somatic mutation in unexplained blood cytopenia. . Blood 129::337178
    [Crossref] [Google Scholar]
  77. 77.
    Mas-Peiro S, Hoffmann J, Fichtlscherer S, Dorsheimer L, Rieger MA, et al. 2019.. Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation. . Eur. Heart J. 41::93339
    [Crossref] [Google Scholar]
  78. 78.
    Miller PG, Qiao D, Rojas-Quintero J, Honigberg MC, Sperling AS, et al. 2022.. Association of clonal hematopoiesis with chronic obstructive pulmonary disease. . Blood 139::35768
    [Crossref] [Google Scholar]
  79. 79.
    Miller PG, Sperling AS, Brea EJ, Leick MB, Fell GG, et al. 2021.. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. . Blood Adv. 5::298286
    [Crossref] [Google Scholar]
  80. 80.
    Mitchell E, Chapman MS, Williams N, Dawson KJ, Mende N, et al. 2022.. Clonal dynamics of haematopoiesis across the human lifespan. . Nature 606::34350
    [Crossref] [Google Scholar]
  81. 81.
    Moore L, Cagan A, Coorens THH, Neville MDC, Sanghvi R, et al. 2021.. The mutational landscape of human somatic and germline cells. . Nature 597::38186
    [Crossref] [Google Scholar]
  82. 82.
    Nachun D, Lu AT, Bick AG, Natarajan P, Weinstock J, et al. 2021.. Clonal hematopoiesis associated with epigenetic aging and clinical outcomes. . Aging Cell 20::e13366
    [Crossref] [Google Scholar]
  83. 83.
    Nahrendorf M. 2018.. Myeloid cell contributions to cardiovascular health and disease. . Nat. Med. 24::71120
    [Crossref] [Google Scholar]
  84. 84.
    Nakamura S, Yokoyama K, Shimizu E, Yusa N, Kondoh K, et al. 2019.. Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS. . Blood 133::268295
    [Crossref] [Google Scholar]
  85. 85.
    Nakao T, Yu Z, Vlasschaert C, Uddin MM, Lindsay ME, et al. 2023.. Increased risk of thoracic aortic aneurysms with JAK2 V617F. . J. Am. Coll. Cardiol. 81::212830
    [Crossref] [Google Scholar]
  86. 86.
    Nam AS, Chaligne R, Landau DA. 2021.. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. . Nat. Rev. Genet. 22::318
    [Crossref] [Google Scholar]
  87. 87.
    Nawas MT, Schetelig J, Damm F, Levine RL, Perales MA, et al. 2021.. The clinical implications of clonal hematopoiesis in hematopoietic cell transplantation. . Blood Rev. 46::100744
    [Crossref] [Google Scholar]
  88. 88.
    Newell LF, Williams T, Liu J, Yu Y, Chen Y, et al. 2021.. Engrafted donor-derived clonal hematopoiesis after allogenic hematopoietic cell transplantation is associated with chronic graft-versus-host disease requiring immunosuppressive therapy, but no adverse impact on overall survival or relapse. . Transplant. Cell Ther. 27::662.e19
    [Crossref] [Google Scholar]
  89. 89.
    Niroula A, Sekar A, Murakami MA, Trinder M, Agrawal M, et al. 2021.. Distinction of lymphoid and myeloid clonal hematopoiesis. . Nat. Med. 27::192127
    [Crossref] [Google Scholar]
  90. 90.
    Nowell PC. 1976.. The clonal evolution of tumor cell populations. . Science 194::2328
    [Crossref] [Google Scholar]
  91. 91.
    Ortmann CA, Dorsheimer L, Abou-El-Ardat K, Hoffrichter J, Assmus B, et al. 2019.. Functional dominance of CHIP-mutated hematopoietic stem cells in patients undergoing autologous transplantation. . Cell Rep. 27::202228.e3
    [Crossref] [Google Scholar]
  92. 92.
    Ostrander EL, Kramer AC, Mallaney C, Celik H, Koh WK, et al. 2020.. Divergent effects of Dnmt3a and Tet2 mutations on hematopoietic progenitor cell fitness. . Stem Cell Rep. 14::55160
    [Crossref] [Google Scholar]
  93. 93.
    Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, et al. (Chronic Myeloid Disord. Work. Group Int. Cancer Genome Consort.). 2013.. Clinical and biological implications of driver mutations in myelodysplastic syndromes. . Blood 122::361627
    [Crossref] [Google Scholar]
  94. 94.
    Pascual-Figal DA, Bayes-Genis A, Díez-Díez M, Hernández-Vicente Á, Vázquez-Andrés D, et al. 2021.. Clonal hematopoiesis and risk of progression of heart failure with reduced left ventricular ejection fraction. . J. Am. Coll. Cardiol. 77::174759
    [Crossref] [Google Scholar]
  95. 95.
    Pasupuleti SK, Ramdas B, Burns SS, Palam LR, Kanumuri R, et al. 2023.. Obesity-induced inflammation exacerbates clonal hematopoiesis. . J. Clin. Investig. 133::e163968
    [Crossref] [Google Scholar]
  96. 96.
    Persani L, Bonomi M, Lleo A, Pasini S, Civardi F, et al. 2012.. Increased loss of the Y chromosome in peripheral blood cells in male patients with autoimmune thyroiditis. . J. Autoimmun. 38::J19396
    [Crossref] [Google Scholar]
  97. 97.
    Pietras EM. 2017.. Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. . Blood 130::169398
    [Crossref] [Google Scholar]
  98. 98.
    Poisson J, Tanguy M, Davy H, Camara F, Mdawar M-BE, et al. 2020.. Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm. . J. Clin. Investig. 130::263043
    [Crossref] [Google Scholar]
  99. 99.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. 2001.. Stem cells, cancer, and cancer stem cells. . Nature 414::10511
    [Crossref] [Google Scholar]
  100. 100.
    Rhee JW, Pillai R, He T, Bosworth A, Chen S, et al. 2024.. Clonal hematopoiesis and cardiovascular disease in patients with multiple myeloma undergoing hematopoietic cell transplant. . JAMA Cardiol. 9::1624
    [Crossref] [Google Scholar]
  101. 101.
    Saini NY, Swoboda DM, Greenbaum U, Ma J, Patel RD, et al. 2022.. Clonal hematopoiesis is associated with increased risk of severe neurotoxicity in axicabtagene ciloleucel therapy of large B-cell lymphoma. . Blood Cancer Discov. 3::38593
    [Crossref] [Google Scholar]
  102. 102.
    Sano S, Oshima K, Wang Y, Katanasaka Y, Sano M, Walsh K. 2018.. CRISPR-mediated gene editing to assess the roles of Tet2 and Dnmt3a in clonal hematopoiesis and cardiovascular disease. . Circ. Res. 123::33541
    [Crossref] [Google Scholar]
  103. 103.
    Sano S, Oshima K, Wang Y, MacLauchlan S, Katanasaka Y, et al. 2018.. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1β/NLRP3 inflammasome. . J. Am. Coll. Cardiol. 71::87586
    [Crossref] [Google Scholar]
  104. 104.
    Sano S, Wang Y, Yura Y, Sano M, Oshima K, et al. 2019.. JAK2V617F-mediated clonal hematopoiesis accelerates pathological remodeling in murine heart failure. . JACC Basic Transl. Sci. 4::68497
    [Crossref] [Google Scholar]
  105. 105.
    Schiller NK, Kubo N, Boisvert WA, Curtiss LK. 2001.. Effect of γ-irradiation and bone marrow transplantation on atherosclerosis in LDL receptor-deficient mice. . Arterioscler. Thrombos. Vasc. Biol. 21::167480
    [Crossref] [Google Scholar]
  106. 106.
    Schuermans A, Vlasschaert C, Nauffal V, Cho SMJ, Uddin MM, et al. 2024.. Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias. . Eur. Heart J. 45::791805
    [Crossref] [Google Scholar]
  107. 107.
    Scolari FL, Abelson S, Brahmbhatt DH, Medeiros JJF, Fan CPS, et al. 2022.. Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock. . Eur. J. Heart Failure 24::157382
    [Crossref] [Google Scholar]
  108. 108.
    Shah NN, Qin H, Yates B, Su L, Shalabi H, et al. 2019.. Clonal expansion of CAR T cells harboring lentivector integration in the CBL gene following anti-CD22 CAR T-cell therapy. . Blood Adv. 3::231722
    [Crossref] [Google Scholar]
  109. 109.
    Shin TH, Zhou Y, Chen S, Cordes S, Grice MZ, et al. 2022.. A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions. . Blood 140::177489
    [Crossref] [Google Scholar]
  110. 110.
    Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, et al. 2014.. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. . Nature 506::32833
    [Crossref] [Google Scholar]
  111. 111.
    Svensson EC, Madar A, Campbell CD, He Y, Sultan M, et al. 2022.. TET2-driven clonal hematopoiesis and response to canakinumab: an exploratory analysis of the CANTOS randomized clinical trial. . JAMA Cardiol. 7::52128
    [Crossref] [Google Scholar]
  112. 112.
    Takahashi K, Wang F, Kantarjian H, Doss D, Khanna K, et al. 2017.. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. . Lancet Oncol. 18::10011
    [Crossref] [Google Scholar]
  113. 113.
    Teipel R, Kroschinsky F, Kramer M, Kretschmann T, Egger-Heidrich K, et al. 2022.. Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment. . Blood Adv. 6::194146
    [Crossref] [Google Scholar]
  114. 114.
    Thompson DJ, Genovese G, Halvardson J, Ulirsch JC, Wright DJ, et al. 2019.. Genetic predisposition to mosaic Y chromosome loss in blood. . Nature 575::65257
    [Crossref] [Google Scholar]
  115. 115.
    Tobias DK, Manning AK, Wessel J, Raghavan S, Westerman KE, et al. 2023.. Clonal hematopoiesis of indeterminate potential (CHIP) and incident type 2 diabetes risk. . Diabetes Care 46::197885
    [Crossref] [Google Scholar]
  116. 116.
    Tomasetti C, Li L, Vogelstein B. 2017.. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. . Science 355::133034
    [Crossref] [Google Scholar]
  117. 117.
    Uddin MDM, Nguyen NQH, Yu B, Brody JA, Pampana A, et al. 2022.. Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease. . Nat. Commun. 13::5350
    [Crossref] [Google Scholar]
  118. 118.
    Valent P. 2019.. ICUS, IDUS, CHIP and CCUS: diagnostic criteria, separation from MDS and clinical implications. . Pathobiology 86::3038
    [Crossref] [Google Scholar]
  119. 119.
    Velasco-Hernandez T, Säwén P, Bryder D, Cammenga J. 2016.. Potential pitfalls of the Mx1-Cre system: implications for experimental modeling of normal and malignant hematopoiesis. . Stem Cell Rep. 7::1118
    [Crossref] [Google Scholar]
  120. 120.
    Walsh R, Jurgens SJ, Erdmann J, Bezzina CR. 2023.. Genome-wide association studies of cardiovascular disease. . Physiol. Rev. 103::203955
    [Crossref] [Google Scholar]
  121. 121.
    Wang J, Li Z, He Y, Pan F, Chen S, et al. 2014.. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice. . Blood 123::54153
    [Crossref] [Google Scholar]
  122. 122.
    Wang S, Hu S, Luo X, Bao X, Li J, et al. 2022.. Prevalence and prognostic significance of DNMT3A- and TET2-clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction. . eBioMedicine 78::103964
    [Crossref] [Google Scholar]
  123. 123.
    Wang W, Liu W, Fidler T, Wang Y, Tang Y, et al. 2018.. Macrophage inflammation, erythrophagocytosis, and accelerated atherosclerosis in Jak2V617F mice. . Circ. Res. 123::e3547
    [Google Scholar]
  124. 124.
    Wang Y, Sano S, Ogawa H, Horitani K, Evans MA, et al. 2022.. Murine models of clonal haematopoiesis to assess mechanisms of cardiovascular disease. . Cardiovasc. Res. 118::141332
    [Crossref] [Google Scholar]
  125. 125.
    Wang Y, Sano S, Yura Y, Ke Z, Sano M, et al. 2020.. Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction. . JCI Insight 5::e135204
    [Crossref] [Google Scholar]
  126. 126.
    Watson CJ, Papula AL, Poon GYP, Wong WH, Young AL, et al. 2020.. The evolutionary dynamics and fitness landscape of clonal hematopoiesis. . Science 367::144954
    [Crossref] [Google Scholar]
  127. 127.
    Weeks LD, Niroula A, Neuberg D, Wong W, Lindsley RC, et al. 2023.. Prediction of risk for myeloid malignancy in clonal hematopoiesis. . NEJM Evid. 2:. https://doi.org/10.1056/EVIDoa2200310
    [Crossref] [Google Scholar]
  128. 128.
    Weinstock JS, Gopakumar J, Burugula BB, Uddin MM, Jahn N, et al. 2023.. Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis. . Nature 616::75563
    [Crossref] [Google Scholar]
  129. 129.
    Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, et al. 2012.. The origin and evolution of mutations in acute myeloid leukemia. . Cell 150::26478
    [Crossref] [Google Scholar]
  130. 130.
    Williams N, Lee J, Mitchell E, Moore L, Baxter EJ, et al. 2022.. Life histories of myeloproliferative neoplasms inferred from phylogenies. . Nature 602::16268
    [Crossref] [Google Scholar]
  131. 131.
    Wolach O, Sellar RS, Martinod K, Cherpokova D, McConkey M, et al. 2018.. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. . Sci. Transl. Med. 10::eaan8292
    [Crossref] [Google Scholar]
  132. 132.
    Wong TN, Miller CA, Jotte MRM, Bagegni N, Baty JD, et al. 2018.. Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential. . Nat. Commun. 9::455
    [Crossref] [Google Scholar]
  133. 133.
    Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, et al. 2015.. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. . Nature 518::55255
    [Crossref] [Google Scholar]
  134. 134.
    Wong WJ, Emdin C, Bick AG, Zekavat SM, Niroula A, et al. 2023.. Clonal haematopoiesis and risk of chronic liver disease. . Nature 616::74754
    [Crossref] [Google Scholar]
  135. 135.
    Woo J, Lu D, Lewandowski A, Xu H, Serrano-Fernandez P, et al. 2023.. Effects of IL-1β inhibition on anemia and clonal hematopoiesis in the randomized CANTOS trial. . Blood Adv. 7::747184
    [Crossref] [Google Scholar]
  136. 135a.
    . 2021.. Cardiovascular diseases (CVDs). . World Health Organization. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
    [Google Scholar]
  137. 136.
    Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, et al. 2014.. Age-related mutations associated with clonal hematopoietic expansion and malignancies. . Nat. Med. 20::147278
    [Crossref] [Google Scholar]
  138. 137.
    Xie Z, Hyun MC, Komrokji RS, Zeidan AM, Madanat YF, et al. 2021.. Characteristics and clinical outcome of patients with clonal cytopenias of undetermined significance: a large retrospective multi-center international study. . Blood 138:(Suppl. 1):2158
    [Crossref] [Google Scholar]
  139. 138.
    Xu JJ, Chalk AM, Wall M, Langdon WY, Smeets MF, Walkley CR. 2022.. Srsf2P95H/+ co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia-like disease in mice. . Leukemia 36::288393
    [Crossref] [Google Scholar]
  140. 139.
    Young AL, Challen GA, Birmann BM, Druley TE. 2016.. Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. . Nat. Commun. 7::12484
    [Crossref] [Google Scholar]
  141. 140.
    Yu B, Roberts MB, Raffield LM, Zekavat SM, Nguyen NQH, et al. 2021.. Supplemental association of clonal hematopoiesis with incident heart failure. . J. Am. Coll. Cardiol. 78::4252
    [Crossref] [Google Scholar]
  142. 141.
    Yu K, Deuitch N, Merguerian M, Cunningham L, Davis J, et al. 2024.. Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy. . Blood Adv. 8::491511
    [Crossref] [Google Scholar]
  143. 142.
    Zekavat SM, Lin S-H, Bick AG, Liu A, Paruchuri K, et al. 2020.. Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. . Nat. Med. 27::101224
    [Crossref] [Google Scholar]
  144. 143.
    Zekavat SM, Viana-Huete V, Matesanz N, Jorshery SD, Zuriaga MA, et al. 2023.. TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease. . Nat. Cardiovasc. Res. 2::14458
    [Crossref] [Google Scholar]
  145. 144.
    Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, et al. 2015.. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. . Nature 525::38993
    [Crossref] [Google Scholar]
  146. 145.
    Zhou Y, Shalhoub R, Rogers SN, Yu S, Gu M, et al. 2022.. Clonal hematopoiesis is not significantly associated with COVID-19 disease severity. . Blood 140::165055
    [Crossref] [Google Scholar]
  147. 146.
    Zink F, Stacey SN, Norddahl GL, Frigge ML, Magnusson OT, et al. 2017.. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. . Blood 130::74252
    [Crossref] [Google Scholar]
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