1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Pathology: Mechanisms of Disease
  4. Volume 19, 2024
  5. Article

Annual Review of Pathology: Mechanisms of Disease

Volume 19, 2024

Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy

Abstract

Somatic or acquired mutations are postzygotic genetic variations that can occur within any tissue. These mutations accumulate during aging and have classically been linked to malignant processes. Tremendous advancements over the past years have led to a deeper understanding of the role of somatic mutations in benign and malignant age-related diseases. Here, we review the somatic mutations that accumulate in the blood and their connection to disease states, with a particular focus on inflammatory diseases and myelodysplastic syndrome. We include a definition of clonal hematopoiesis (CH) and an overview of the origins and implications of these mutations. In addition, we emphasize somatic disorders with overlapping inflammation and hematologic disease beyond CH, including paroxysmal nocturnal hemoglobinuria and aplastic anemia, focusing on VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Finally, we provide a practical view of the implications of somatic mutations in clinical hematology, pathology, and beyond.

Keyword(s): autoimmune, clonal hematopoiesis, inflammation, MDS, myelodysplastic syndrome, plasma cell neoplasm, UBA1, VEXAS
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathmechdis-051222-122724
2024-01-24
2024-04-29
Loading full text...

Full text loading...

/deliver/fulltext/pathol/19/1/annurev-pathmechdis-051222-122724.html?itemId=/content/journals/10.1146/annurev-pathmechdis-051222-122724&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Mustjoki S, Young NS. 2021. Somatic mutations in “benign” disease. N. Engl. J. Med. 384:2039–52
     [Google Scholar]
  2. 2.
    Cagan A, Baez-Ortega A, Brzozowska N, Abascal F, Coorens THH et al. 2022. Somatic mutation rates scale with lifespan across mammals. Nature 604:517–24
     [Google Scholar]
  3. 3.
    Jaiswal S, Ebert BL. 2019. Clonal hematopoiesis in human aging and disease. Science 366:eaan4673
     [Google Scholar]
  4. 4.
    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. 371:2488–98
     [Google Scholar]
  5. 5.
    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. 377:111–21
     [Google Scholar]
  6. 6.
    Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA et al. 2015. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood J. Am. Soc. Hematol. 126:9–16
     [Google Scholar]
  7. 7.
    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. 371:2477–87
     [Google Scholar]
  8. 8.
    Hecker JS, Hartmann L, Rivière J, Buck MC, van der Garde M et al. 2021. CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease. Blood 138:1727–32
     [Google Scholar]
  9. 9.
    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 36:1703–19
     [Google Scholar]
  10. 10.
    Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR et al. 2022. International Consensus Classification of Myeloid Neoplasms and Acute Leukemia: integrating morphological, clinical, and genomic data. Blood 140:111200–28
     [Google Scholar]
  11. 11.
    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. 20:1472–78
     [Google Scholar]
  12. 12.
    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 355:842–47
     [Google Scholar]
  13. 13.
    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. 71:875–86
     [Google Scholar]
  14. 14.
    Bick AG, Pirruccello JP, Griffin GK, Gupta N, Gabriel S et al. 2020. Genetic interleukin 6 signaling deficiency attenuates cardiovascular risk in clonal hematopoiesis. Circulation 141:124–31
     [Google Scholar]
  15. 15.
    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. 18:100–11
     [Google Scholar]
  16. 16.
    Steensma DP. 2018. Clinical consequences of clonal hematopoiesis of indeterminate potential. Blood Adv. 2:3404–10
     [Google Scholar]
  17. 17.
    Bewersdorf JP, Ardasheva A, Podoltsev NA, Singh A, Biancon G et al. 2019. From clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities?. Blood Rev. 37:100587
     [Google Scholar]
  18. 18.
    Xie Z, Zeidan AM. 2023. CHIPing away the progression potential of CHIP: a new reality in the making. Blood Rev. 58:101001
     [Google Scholar]
  19. 19.
    Bejar R. 2017. CHIP, ICUS, CCUS and other four-letter words. Leukemia 31:1869–71
     [Google Scholar]
  20. 20.
    Shlush LI. 2018. Age-related clonal hematopoiesis. Blood J. Am. Soc. Hematol. 131:496–504
     [Google Scholar]
  21. 21.
    Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR. 2023. The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia. Virchows Arch. 482:113–30
     [Google Scholar]
  22. 22.
    Garcia-Manero G, Chien KS, Montalban-Bravo G. 2020. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am. J. Hematol. 95:1399–420
     [Google Scholar]
  23. 23.
    Li H, Hu F, Gale RP, Sekeres MA, Liang Y. 2022. Myelodysplastic syndromes. Nat. Rev. Dis. Primers 8:74
     [Google Scholar]
  24. 24.
    Severson EA, Riedlinger GM, Connelly CF, Vergilio J-A, Goldfinger M et al. 2018. Detection of clonal hematopoiesis of indeterminate potential in clinical sequencing of solid tumor specimens. Blood J. Am. Soc. Hematol. 131:2501–5
     [Google Scholar]
  25. 25.
    Kwan TT, Oza AM, Tinker AV, Ray-Coquard I, Oaknin A et al. 2021. Preexisting TP53-variant clonal hematopoiesis and risk of secondary myeloid neoplasms in patients with high-grade ovarian cancer treated with rucaparib. JAMA Oncol. 7:1772–81
     [Google Scholar]
  26. 26.
    Razavi P, Li BT, Brown DN, Jung B, Hubbell E et al. 2019. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat. Med. 25:1928–37
     [Google Scholar]
  27. 27.
    McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H et al. 2015. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 10:1239–45
     [Google Scholar]
  28. 28.
    Mei Y, Zhao B, Basiorka A, Yang J, Cao L et al. 2018. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del (5q) MDS. Leukemia 32:1023–33
     [Google Scholar]
  29. 29.
    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 J. Am. Soc. Hematol. 130:742–52
     [Google Scholar]
  30. 30.
    Bick AG, Weinstock JS, Nandakumar SK, Fulco CP, Bao EL et al. 2020. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 586:763–68
     [Google Scholar]
  31. 31.
    Bolton KL, Ptashkin RN, Gao T, Braunstein L, Devlin SM et al. 2020. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat. Genet. 52:1219–26
     [Google Scholar]
  32. 32.
    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. 18:100–11
     [Google Scholar]
  33. 33.
    Kahn JD, Miller PG, Silver AJ, Sellar RS, Bhatt S et al. 2018. PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells. Blood J. Am. Soc. Hematol. 132:1095–105
     [Google Scholar]
  34. 34.
    Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K et al. 2015. Somatic mutations and clonal hematopoiesis in aplastic anemia. N. Engl. J. Med. 373:35–47
     [Google Scholar]
  35. 35.
    Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC et al. 2020. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 383:2628–38
     [Google Scholar]
  36. 36.
    Obiorah IE, Patel BA, Groarke EM, Wang W, Trick M et al. 2021. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Adv. 5:3203–15
     [Google Scholar]
  37. 37.
    Patel N, Dulau-Florea A, Calvo KR. 2021. Characteristic bone marrow findings in patients with UBA1 somatic mutations and VEXAS syndrome. Semin. Hematol. 58:204–11
     [Google Scholar]
  38. 38.
    Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B et al. 2021. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS. Arthritis Rheumatol. 73:1886–95
     [Google Scholar]
  39. 39.
    Savola P, Lundgren S, Keränen MAI, Almusa H, Ellonen P et al. 2018. Clonal hematopoiesis in patients with rheumatoid arthritis. Blood Cancer J. 8:869 Erratum 2021. Blood Cancer J. 11:36
     [Google Scholar]
  40. 40.
    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:e264–67
     [Google Scholar]
  41. 41.
    Gutierrez-Rodrigues F, Jones AI, Wells K, Hironaka D, Rankin C et al. 2022. Clonal hematopoiesis in a broad age spectrum of systemic vasculitis. Blood 140:8596–97
     [Google Scholar]
  42. 42.
    David C, Duployez N, Eloy P, Belhadi D, Chezel J et al. 2022. Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study). Rheumatology 61:4355–63
     [Google Scholar]
  43. 43.
    Valori M, Jansson L, Tienari PJ. 2021. CD8+ cell somatic mutations in multiple sclerosis patients and controls—enrichment of mutations in STAT3 and other genes implicated in hematological malignancies. PLOS ONE 16:e0261002
     [Google Scholar]
  44. 44.
    Cumbo C, Tarantini F, Zagaria A, Anelli L, Minervini CF et al. 2022. Clonal hematopoiesis at the crossroads of inflammatory bowel diseases and hematological malignancies: a biological link?. Front. Oncol. 12:873896
     [Google Scholar]
  45. 45.
    Marshall CH, Gondek LP, Luo J, Antonarakis ES. 2022. Clonal hematopoiesis of indeterminate potential in patients with solid tumor malignancies. Cancer Res. 82:4107–13
     [Google Scholar]
  46. 46.
    Weber-Lassalle K, Harter P, Hauke J, Ernst C, Kommoss S et al. 2018. Diagnosis of Li-Fraumeni syndrome: differentiating TP53 germline mutations from clonal hematopoiesis: results of the observational AGO-TR1 trial. Hum. Mutat. 39:2040–46
     [Google Scholar]
  47. 47.
    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
     [Google Scholar]
  48. 48.
    Weitzel JN, Chao EC, Nehoray B, Van Tongeren LR, LaDuca H et al. 2018. Somatic TP53 variants frequently confound germ-line testing results. Genet. Med. 20:809–16
     [Google Scholar]
  49. 49.
    Gill J, Obley AJ, Prasad V. 2018. Direct-to-consumer genetic testing: the implications of the US FDA's first marketing authorization for BRCA mutation testing. JAMA 319:2377–78
     [Google Scholar]
  50. 50.
    Bolton KL, Ptashkin RN, Gao T, Braunstein L, Devlin SM et al. 2020. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat. Genet. 52:1219–26
     [Google Scholar]
  51. 51.
    van Zeventer IA, Salzbrunn JB, de Graaf AO, van der Reijden BA, Boezen HM et al. 2021. Prevalence, predictors, and outcomes of clonal hematopoiesis in individuals aged ≥80 years. Blood Adv. 5:2115–22
     [Google Scholar]
  52. 52.
    Loh P-R, Genovese G, Handsaker RE, Finucane HK, Reshef YA et al. 2018. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 559:350–55
     [Google Scholar]
  53. 53.
    Vattathil S, Scheet P. 2016. Extensive hidden genomic mosaicism revealed in normal tissue. Am. J. Hum. Genet. 98:571–78
     [Google Scholar]
  54. 54.
    Bonnefond A, Skrobek B, Lobbens S, Eury E, Thuillier D et al. 2013. Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications. Nat. Genet. 45:1040–43
     [Google Scholar]
  55. 55.
    Jacobs KB, Yeager M, Zhou W, Wacholder S, Wang Z et al. 2012. Detectable clonal mosaicism and its relationship to aging and cancer. Nat. Genet. 44:651–58
     [Google Scholar]
  56. 56.
    Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB et al. 2015. Characterization of large structural genetic mosaicism in human autosomes. Am. J. Hum. Genet. 96:487–97
     [Google Scholar]
  57. 57.
    Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR et al. 2012. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat. Genet. 44:642–50
     [Google Scholar]
  58. 58.
    Sudlow C, Gallacher J, Allen N, Beral V, Burton P et al. 2015. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLOS Med. 12:e1001779
     [Google Scholar]
  59. 59.
    Yang H, Garcia-Manero G, Sasaki K, Montalban-Bravo G, Tang Z et al. 2022. High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance. Leukemia 36:2306–16
     [Google Scholar]
  60. 60.
    Smith AC, Neveling K, Kanagal-Shamanna R. 2022. Optical genome mapping for structural variation analysis in hematologic malignancies. Am. J. Hematol. 97:975–82
     [Google Scholar]
  61. 61.
    Levy B, Baughn LB, Akkari YMN, Chartrand S, LaBarge B et al. 2022. Optical genome mapping in acute myeloid leukemia: a multicenter evaluation. Blood Adv. 7:1297–307
     [Google Scholar]
  62. 62.
    Lestringant V, Duployez N, Penther D, Luquet I, Derrieux C et al. 2021. Optical genome mapping, a promising alternative to gold standard cytogenetic approaches in a series of acute lymphoblastic leukemias. Genes Chromosomes Cancer 60:657–67
     [Google Scholar]
  63. 63.
    Neveling K, Mantere T, Vermeulen S, Oorsprong M, van Beek R et al. 2021. Next-generation cytogenetics: comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping. Am. J. Hum. Genet. 108:1423–35
     [Google Scholar]
  64. 64.
    Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S et al. 2021. Genome sequencing as an alternative to cytogenetic analysis in myeloid cancers. N. Engl. J. Med. 384:924–35
     [Google Scholar]
  65. 65.
    Haferlach T, Hutter S, Meggendorfer M. 2021. Genome sequencing in myeloid cancers. N. Engl. J. Med. 384:e106
     [Google Scholar]
  66. 66.
    Mitchell E, Spencer Chapman M, Williams N, Dawson KJ, Mende N et al. 2022. Clonal dynamics of haematopoiesis across the human lifespan. Nature 606:343–50
     [Google Scholar]
  67. 67.
    Jain P, Binder AM, Chen B, Parada H Jr., Gallo LC et al. 2022. Analysis of epigenetic age acceleration and healthy longevity among older US women. JAMA Netw. Open 5:e2223285
     [Google Scholar]
  68. 68.
    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
     [Google Scholar]
  69. 69.
    Hannum G, Guinney J, Zhao L, Zhang L, Hughes G et al. 2013. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49:359–67
     [Google Scholar]
  70. 70.
    Irvin MR, Aslibekyan S, Do A, Zhi D, Hidalgo B et al. 2018. Metabolic and inflammatory biomarkers are associated with epigenetic aging acceleration estimates in the GOLDN study. Clin. Epigenet. 10:56
     [Google Scholar]
  71. 71.
    Rossi M, Meggendorfer M, Zampini M, Tettamanti M, Riva E et al. 2021. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years. Blood 138:2093–105
     [Google Scholar]
  72. 72.
    Silver AJ, Bick AG, Savona MR. 2021. Germline risk of clonal haematopoiesis. Nat. Rev. Genet. 22:603–17
     [Google Scholar]
  73. 73.
    Thompson DJ, Genovese G, Halvardson J, Ulirsch JC, Wright DJ et al. 2019. Genetic predisposition to mosaic Y chromosome loss in blood. Nature 575:652–57
     [Google Scholar]
  74. 74.
    Hinds DA, Barnholt KE, Mesa RA, Kiefer AK, Do CB et al. 2016. Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. Blood 128:1121–28
     [Google Scholar]
  75. 75.
    West RR, Calvo KR, Embree LJ, Wang W, Tuschong LM et al. 2022. ASXL1 and STAG2 are common mutations in GATA2 deficiency patients with bone marrow disease and myelodysplastic syndrome. Blood Adv. 6:793–807
     [Google Scholar]
  76. 76.
    Churpek JE, Pyrtel K, Kanchi KL, Shao J, Koboldt D et al. 2015. Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood 126:2484–90
     [Google Scholar]
  77. 77.
    Warren JT, Link DC. 2020. Clonal hematopoiesis and risk for hematologic malignancy. Blood 136:1599–605
     [Google Scholar]
  78. 78.
    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 21:374–82.e4
     [Google Scholar]
  79. 79.
    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. 18:112–21
     [Google Scholar]
  80. 80.
    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 518:552–55
     [Google Scholar]
  81. 81.
    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 23:700–13.e6
     [Google Scholar]
  82. 82.
    Lindsley RC, Saber W, Mar BG, Redd R, Wang T et al. 2017. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N. Engl. J. Med. 376:536–47
     [Google Scholar]
  83. 83.
    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
     [Google Scholar]
  84. 84.
    Jasra S, Giricz O, Zeig-Owens R, Pradhan K, Goldfarb DG et al. 2022. High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster. Nat. Med. 28:468–71
     [Google Scholar]
  85. 85.
    King KY, Huang Y, Nakada D, Goodell MA. 2020. Environmental influences on clonal hematopoiesis. Exp. Hematol. 83:66–73
     [Google Scholar]
  86. 86.
    Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM et al. 2018. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557:580–84
     [Google Scholar]
  87. 87.
    Wei Y, Kanagal-Shamanna R, Zheng H, Bao N, Lockyer PP et al. 2022. Cooperation between KDM6B overexpression and TET2 deficiency in the pathogenesis of chronic myelomonocytic leukemia. Leukemia 36:2097–107
     [Google Scholar]
  88. 88.
    Cai Z, Kotzin JJ, Ramdas B, Chen S, Nelanuthala S et al. 2018. Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis. Cell Stem Cell 23:833–49.e5
     [Google Scholar]
  89. 89.
    Abegunde SO, Buckstein R, Wells RA, Rauh MJ. 2018. An inflammatory environment containing TNFα favors Tet2-mutant clonal hematopoiesis. Exp. Hematol. 59:60–65
     [Google Scholar]
  90. 90.
    Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC et al. 2011. Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. PNAS 108:14566–71
     [Google Scholar]
  91. 91.
    Challen GA, Sun D, Jeong M, Luo M, Jelinek J et al. 2011. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat. Genet. 44:23–31
     [Google Scholar]
  92. 92.
    Guryanova OA, Shank K, Spitzer B, Luciani L, Koche RP et al. 2016. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat. Med. 22:1488–95
     [Google Scholar]
  93. 93.
    Cole CB, Russler-Germain DA, Ketkar S, Verdoni AM, Smith AM et al. 2017. Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies. J. Clin. Investig. 127:3657–74
     [Google Scholar]
  94. 94.
    Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D et al. 2011. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20:11–24
     [Google Scholar]
  95. 95.
    Celik H, Mallaney C, Kothari A, Ostrander EL, Eultgen E et al. 2015. Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic transformation. Blood 125:619–28
     [Google Scholar]
  96. 96.
    Brodsky RA. 2014. Paroxysmal nocturnal hemoglobinuria. Blood 124:2804–11
     [Google Scholar]
  97. 97.
    Fabre MA, de Almeida JG, Fiorillo E, Mitchell E, Damaskou A et al. 2022. The longitudinal dynamics and natural history of clonal haematopoiesis. Nature 606:335–42
     [Google Scholar]
  98. 98.
    Watson CJ, Papula A, Poon GY, Wong WH, Young AL et al. 2020. The evolutionary dynamics and fitness landscape of clonal hematopoiesis. Science 367:1449–54
     [Google Scholar]
  99. 99.
    Ridker PM. 2016. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ. Res. 118:145–56
     [Google Scholar]
  100. 100.
    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. 78:42–52
     [Google Scholar]
  101. 101.
    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. 123:335–41
     [Google Scholar]
  102. 102.
    Everett BM, Cornel JH, Lainscak M, Anker SD, Abbate A et al. 2019. Anti-inflammatory therapy with canakinumab for the prevention of hospitalization for heart failure. Circulation 139:1289–99
     [Google Scholar]
  103. 103.
    Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH et al. 2017. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377:1119–31
     [Google Scholar]
  104. 104.
    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. 7:521–28
     [Google Scholar]
  105. 105.
    Libby P. 2017. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J. Am. Coll. Cardiol. 70:2278–89
     [Google Scholar]
  106. 106.
    Asada S, Kitamura T. 2021. Clonal hematopoiesis and associated diseases: a review of recent findings. Cancer Sci. 112:3962–71
     [Google Scholar]
  107. 107.
    Muto T, Walker CS, Choi K, Hueneman K, Smith MA et al. 2020. Adaptive response to inflammation contributes to sustained myelopoiesis and confers a competitive advantage in myelodysplastic syndrome HSCs. Nat. Immunol. 21:535–45
     [Google Scholar]
  108. 108.
    Agrawal M, Niroula A, Cunin P, McConkey M, Shkolnik V et al. 2022. TET2-mutant clonal hematopoiesis and risk of gout. Blood 140:1094–103
     [Google Scholar]
  109. 109.
    Merriman TR, Joosten LAB. 2022. CHIP and gout: trained immunity?. Blood 140:1054–56
     [Google Scholar]
  110. 110.
    Georgin-Lavialle S, Terrier B, Guedon AF, Heiblig M, Comont T et al. 2022. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br. J. Dermatol. 186:564–74
     [Google Scholar]
  111. 111.
    Ferrada MA, Savic S, Cardona DO, Collins JC, Alessi H et al. 2022. Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis. Blood 140:1496–506
     [Google Scholar]
  112. 112.
    Sharma A, Naidu G, Deo P, Beck DB. 2022. VEXAS syndrome with systemic lupus erythematosus: expanding the spectrum of associated conditions. Arthritis Rheumatol. 74:369–71
     [Google Scholar]
  113. 113.
    Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J et al. 2023. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population. JAMA 329:318–24
     [Google Scholar]
  114. 114.
    Manthiram K, Zhou Q, Aksentijevich I, Kastner DL. 2017. The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat. Immunol. 18:832–42
     [Google Scholar]
  115. 115.
    Cherniawsky H, Friedmann J, Nicolson H, Dehghan N, Stubbins RJ et al. 2023. VEXAS syndrome: a review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation. Eur. J. Haematol. 110:633–38
     [Google Scholar]
  116. 116.
    Delaleu J, Kim R, Zhao LP, de Masson A, Vignon-Pennamen MD et al. 2022. Clinical, pathological, and molecular features of myelodysplasia cutis. Blood 139:1251–53
     [Google Scholar]
  117. 117.
    Jin J, Li X, Gygi SP, Harper JW. 2007. Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. Nature 447:1135–38
     [Google Scholar]
  118. 118.
    Hyer ML, Milhollen MA, Ciavarri J, Fleming P, Traore T et al. 2018. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat. Med. 24:186–93
     [Google Scholar]
  119. 119.
    Sakuma M, Blombery P, Meggendorfer M, Haferlach C, Lindauer M et al. 2023. Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies. Leukemia 37:1080–91
     [Google Scholar]
  120. 120.
    Bourbon E, Heiblig M, Gerfaud Valentin M, Barba T, Durel CA et al. 2021. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 137:3682–84
     [Google Scholar]
  121. 121.
    Battipaglia G, Vincenzi A, Falconi G, Fiore A, D'Agostino F et al. 2023. New scenarios in Vacuoles, E1 enzyme, X linked, Autoinflammatory, Somatic (VEXAS) syndrome: evolution from myelodysplastic syndrome to acute myeloid leukemia. Curr. Res. Transl. Med. 71:103386
     [Google Scholar]
  122. 122.
    Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shahloub R et al. 2023. The spectrum of clonal hematopoiesis in VEXAS syndrome. Blood 142:244–59
     [Google Scholar]
  123. 123.
    Austestad J, Madland TM, Sandnes M, Haslerud TM, Benneche A, Reikvam H. 2023. VEXAS syndrome in a patient with myeloproliferative neoplasia. Case Rep. Hematol. 2023:6551544
     [Google Scholar]
  124. 124.
    Neupane K, Jayarangaiah A, Zhang Y, Kumar A. 2022. VEXAS syndrome with progression of MDS to MDS/MPN overlap syndrome. BMJ Case Rep. 15:e251089
     [Google Scholar]
  125. 125.
    Al-Hakim A, Poulter JA, Mahmoud D, Rose AMS, Elcombe S et al. 2022. Allogeneic haematopoietic stem cell transplantation for VEXAS syndrome: UK experience. Br. J. Haematol. 199:777–81
     [Google Scholar]
  126. 126.
    Mangaonkar AA, Langer KJ, Lasho TL, Finke C, Litzow MR et al. 2023. Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in VEXAS syndrome: data from a prospective series of patients. Am. J. Hematol. 98:E28–31
     [Google Scholar]
  127. 127.
    Loschi M, Roux C, Sudaka I, Ferrero-Vacher C, Marceau-Renaut A et al. 2022. Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: a case report. Bone Marrow Transplant 57:315–18
     [Google Scholar]
  128. 128.
    Oganesyan A, Hakobyan Y, Terrier B, Georgin-Lavialle S, Mekinian A. 2021. Looking beyond VEXAS: coexistence of undifferentiated systemic autoinflammatory disease and myelodysplastic syndrome. Semin. Hematol. 58:247–53
     [Google Scholar]
  129. 129.
    Komrokji RS, Kulasekararaj A, Al Ali NH, Kordasti S, Bart-Smith E et al. 2016. Autoimmune diseases and myelodysplastic syndromes. Am. J. Hematol. 91:E280–83
     [Google Scholar]
  130. 130.
    Louvrier C, Assrawi E, El Khouri E, Melki I, Copin B et al. 2020. NLRP3-associated autoinflammatory diseases: Phenotypic and molecular characteristics of germline versus somatic mutations. J. Allergy Clin. Immunol. 145:1254–61
     [Google Scholar]
  131. 131.
    van der Made CI, Potjewijd J, Hoogstins A, Willems HPJ, Kwakernaak AJ et al. 2022. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS. J. Allergy Clin. Immunol. 149:432–39.e4
     [Google Scholar]
  132. 132.
    Gurnari C, Pagliuca S, Durkin L, Terkawi L, Awada H et al. 2021. Vacuolization of hematopoietic precursors: an enigma with multiple etiologies. Blood 137:3685–89
     [Google Scholar]
  133. 133.
    Tsuchida N, Kunishita Y, Uchiyama Y, Kirino Y, Enaka M et al. 2021. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann. Rheum. Dis. 80:1057–61
     [Google Scholar]
  134. 134.
    Olteanu H, Patnaik M, Koster M, Warrington K, Go R et al. 2023. Comprehensive characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome reveals distinct morphologic diagnostic features: a single-institution longitudinal study of 94 cases from 42 individuals. Lab. Investig. 103:S1214–15 ( USCAP 2023 Abstr. Hematopathol. )
     [Google Scholar]
  135. 135.
    Rabut A, Jasserand L, Richard C, Dumas C, Mestrallet F et al. 2023. Quantitative assessment of vacuolization of myeloid precursors in VEXAS syndrome. Hemasphere 7:e828
     [Google Scholar]
  136. 136.
    Matsumoto H, Fujita Y, Fukatsu M, Ikezoe T, Yokose K et al. 2022. Case report: coexistence of multiple myeloma and auricular chondritis in VEXAS syndrome. Front. Immunol. 13:897722
     [Google Scholar]
  137. 137.
    Carrel L, Clemson CM, Dunn JM, Miller AP, Hunt PA et al. 1996. X inactivation analysis and DNA methylation studies of the ubiquitin activating enzyme E1 and PCTAIRE-1 genes in human and mouse. Hum. Mol. Genet. 5:391–401
     [Google Scholar]
  138. 138.
    Barba T, Jamilloux Y, Durel CA, Bourbon E, Mestrallet F et al. 2021. VEXAS syndrome in a woman. Rheumatology 60:e402–3
     [Google Scholar]
  139. 139.
    Stubbins RJ, McGinnis E, Johal B, Chen LY, Wilson L et al. 2022. VEXAS syndrome in a female patient with constitutional 45,X (Turner syndrome). Haematologica 107:1011–13
     [Google Scholar]
  140. 140.
    Arlet JB, Terrier B, Kosmider O. 2021. Mutant UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 384:2163
     [Google Scholar]
  141. 141.
    Luzzatto L, Risitano AM, Notaro R. 2021. Mutant UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 384:2164
     [Google Scholar]
  142. 142.
    Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y et al. 1993. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73:703–11
     [Google Scholar]
  143. 143.
    Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K et al. 2015. Somatic mutations and clonal hematopoiesis in aplastic anemia. N. Engl. J. Med. 373:35–47
     [Google Scholar]
  144. 144.
    Singhal R, Chawla S, Rathore DK, Bhasym A, Annarapu GK et al. 2017. Development of pro-inflammatory phenotype in monocytes after engulfing Hb-activated platelets in hemolytic disorders. Clin. Immunol. 175:133–42
     [Google Scholar]
  145. 145.
    Consonni F, Gambineri E, Favre C. 2022. ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies. Ann. Hematol. 101:469–84
     [Google Scholar]
  146. 146.
    Oliveira JB, Bidère N, Niemela JE, Zheng L, Sakai K et al. 2007. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. PNAS 104:8953–58
     [Google Scholar]
  147. 147.
    Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I et al. 2011. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. Blood 117:2883–86
     [Google Scholar]
  148. 148.
    Calvo KR, Price S, Braylan RC, Oliveira JB, Lenardo M et al. 2015. JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities. Blood 125:2753–58
     [Google Scholar]
  149. 149.
    Lanzarotti N, Bruneau J, Trinquand A, Stolzenberg MC, Neven B et al. 2014. RAS-associated lymphoproliferative disease evolves into severe juvenile myelo-monocytic leukemia. Blood 123:1960–63
     [Google Scholar]
  150. 150.
    Haroche J, Cohen-Aubart F, Amoura Z. 2020. Erdheim-Chester disease. Blood 135:1311–18
     [Google Scholar]
  151. 151.
    Savola P, Brück O, Olson T, Kelkka T, Kauppi MJ et al. 2018. Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia. Haematologica 103:304–12
     [Google Scholar]
  152. 152.
    Reiter A, Gotlib J. 2017. Myeloid neoplasms with eosinophilia. Blood 129:704–14
     [Google Scholar]
  153. 153.
    Singh M, Jackson KJL, Wang JJ, Schofield P, Field MA et al. 2020. Lymphoma driver mutations in the pathogenic evolution of an iconic human autoantibody. Cell 180:878–94.e19
     [Google Scholar]
  154. 154.
    Nanki K, Fujii M, Shimokawa M, Matano M, Nishikori S et al. 2020. Somatic inflammatory gene mutations in human ulcerative colitis epithelium. Nature 577:254–59
     [Google Scholar]
  155. 155.
    Pei C, Cui Q, Zhao Q, Liu Y, Wang C, Jing L. 2020. Reference value of magnetic resonance imaging and echocardiography in the diagnosis of pulmonary hypertension at high altitude. Minerva Med. https://doi.org/10.23736/S0026-4806.20.06760-9
    [Crossref] [Google Scholar]
  156. 156.
    Kakiuchi N, Yoshida K, Uchino M, Kihara T, Akaki K et al. 2020. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature 577:260–65
     [Google Scholar]
  157. 157.
    Gruber CN, Calis JJA, Buta S, Evrony G, Martin JC et al. 2020. Complex autoinflammatory syndrome unveils fundamental principles of JAK1 kinase transcriptional and biochemical function. Immunity 53:672–84.e11
     [Google Scholar]
  158. 158.
    Olafsson S, Anderson CA. 2021. Somatic mutations provide important and unique insights into the biology of complex diseases. Trends Genet. 37:872–81
     [Google Scholar]
  159. 159.
    Kristinsson SY, Björkholm M, Hultcrantz M, Derolf ÅR, Landgren O, Goldin LR. 2011. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J. Clin. Oncol. 29:2897
     [Google Scholar]
  160. 160.
    Barreyro L, Chlon TM, Starczynowski DT. 2018. Chronic immune response dysregulation in MDS pathogenesis. Blood J. Am. Soc. Hematol. 132:1553–60
     [Google Scholar]
  161. 161.
    Stubbins RJ, Platzbecker U, Karsan A. 2022. Inflammation and myeloid malignancy: quenching the flame. Blood 140:1067–74
     [Google Scholar]
  162. 162.
    Franco I, Revêchon G, Eriksson M. 2022. Challenges of proving a causal role of somatic mutations in the aging process. Aging Cell 21:e13613
     [Google Scholar]
  163. 163.
    Garcia-Manero G. 2023. Current status of phase 3 clinical trials in high-risk myelodysplastic syndromes: pitfalls and recommendations. Lancet Haematol. 10:e71–78
     [Google Scholar]
  164. 164.
    Sallman DA, Cluzeau T, Basiorka AA, List A. 2016. Unraveling the pathogenesis of MDS: the NLRP3 inflammasome and pyroptosis drive the MDS phenotype. Front. Oncol. 6:151
     [Google Scholar]
  165. 165.
    Sallman DA, List A. 2019. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood 133:1039–48
     [Google Scholar]
  166. 166.
    Gañán-Gómez I, Wei Y, Starczynowski D, Colla S, Yang H et al. 2015. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia 29:1458–69
     [Google Scholar]
  167. 167.
    Sallman DA, List A. 2019. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood J. Am. Soc. Hematol. 133:1039–48
     [Google Scholar]
  168. 168.
    Wei Y, Dimicoli S, Bueso-Ramos C, Chen R, Yang H et al. 2013. Toll-like receptor alterations in myelodysplastic syndrome. Leukemia 27:1832–40
     [Google Scholar]
  169. 169.
    Rhyasen GW, Bolanos L, Fang J, Jerez A, Wunderlich M et al. 2013. Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome. Cancer Cell 24:90–104
     [Google Scholar]
  170. 170.
    Broz P, Dixit VM. 2016. Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16:407–20
     [Google Scholar]
  171. 171.
    Malik A, Kanneganti T-D. 2017. Inflammasome activation and assembly at a glance. J. Cell Sci. 130:3955–63
     [Google Scholar]
  172. 172.
    de Carvalho Ribeiro M, Szabo G. 2022. Role of the inflammasome in liver disease. Annu. Rev. Pathol. Mech. Dis. 17:345–65
     [Google Scholar]
  173. 173.
    Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R et al. 2020. Luspatercept in patients with lower-risk myelodysplastic syndromes. N. Engl. J. Med. 382:140–51
     [Google Scholar]
  174. 174.
    Gonzalez-Lugo JD, Verma A. 2022. Targeting inflammation in lower-risk MDS. Hematol. Am. Soc. Hematol. Educ. Program. 2022:382–87
     [Google Scholar]
  175. 175.
    Garcia-Manero G, Mufti GJ, Fenaux P, Buckstein R, Santini V et al. 2022. Neutrophil and platelet increases with luspatercept in lower-risk MDS: secondary endpoints from the MEDALIST trial. Blood 139:624–29
     [Google Scholar]
  176. 176.
    Rodriguez-Sevilla JJ, Adema V, Garcia-Manero G, Colla S. 2023. Emerging treatments for myelodysplastic syndromes: biological rationales and clinical translation. Cell Rep. Med. 4:100940
     [Google Scholar]
  177. 177.
    Garcia-Manero G, Jabbour EJ, Konopleva MY, Daver NG, Borthakur G et al. 2018. A clinical study of tomaralimab (OPN-305), a Toll-like receptor 2 (TLR-2) antibody, in heavily pre-treated transfusion dependent patients with lower risk myelodysplastic syndromes (MDS) that have received and failed on prior hypomethylating agent (HMA) therapy. Blood 132:798
     [Google Scholar]
  178. 178.
    Garcia-Manero G, Winer ES, DeAngelo DJ, Tarantolo SR, Sallman DA et al. 2022. Phase 1/2a study of the IRAK4 inhibitor CA-4948 as monotherapy or in combination with azacitidine or venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia or lyelodysplastic syndrome. Am. Soc. Clin. Oncol. 40:16, Suppl.7016 Abstr. )
     [Google Scholar]
  179. 179.
    Naqvi K, Garcia-Manero G, Sardesai S, Oh J, Vigil CE et al. 2011. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J. Clin. Oncol. 29:2240
     [Google Scholar]
  180. 180.
    Naqvi K, Sasaki K, Montalban-Bravo G, Alfonso Pierola A, Yilmaz M et al. 2019. Clonal hematopoiesis of indeterminate potential—associated mutations and risk of comorbidities in patients with myelodysplastic syndrome. Cancer 125:2233–41
     [Google Scholar]
  181. 181.
    Weeks LD, Niroula A, Neuberg DS, Wong WJ, Lindsley RC et al. 2022. Prediction of risk for myeloid malignancy in clonal hematopoiesis. Blood 140:2229–31
     [Google Scholar]
  182. 182.
    Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N et al. 2018. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 559:400–4
     [Google Scholar]
  183. 183.
    Malcovati L, Galli A, Travaglino E, Ambaglio I, Rizzo E et al. 2017. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 129:3371–78
     [Google Scholar]
  184. 184.
    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. 24:1015–23
     [Google Scholar]
  185. 185.
    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. 35:1598–605
     [Google Scholar]
  186. 186.
    Malcovati L, Stevenson K, Papaemmanuil E, Neuberg D, Bejar R et al. 2020. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood 136:157–70
     [Google Scholar]
  187. 187.
    Kanagal-Shamanna R, Montalban-Bravo G, Sasaki K, Darbaniyan F, Jabbour E et al. 2021. Only SF3B1 mutation involving K700E independently predicts overall survival in myelodysplastic syndromes. Cancer 127:3552–65
     [Google Scholar]
  188. 188.
    Dalton WB, Helmenstine E, Pieterse L, Li B, Gocke CD et al. 2020. The K666N mutation in SF3B1 is associated with increased progression of MDS and distinct RNA splicing. Blood Adv. 4:1192–96
     [Google Scholar]
  189. 189.
    Cargo CA, Rowbotham N, Evans PA, Barrans SL, Bowen DT et al. 2015. Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. Blood 126:2362–65
     [Google Scholar]
  190. 190.
    Kwok B, Hall JM, Witte JS, Xu Y, Reddy P et al. 2015. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood 126:2355–61
     [Google Scholar]
  191. 191.
    Jumniensuk C, Nobori A, Lee T, Senaratne TN, Rao D, Pullarkat S. 2022. Concordance of peripheral blood and bone marrow next-generation sequencing in hematologic neoplasms. Adv. Hematol. 2022:8091746
     [Google Scholar]
  192. 192.
    Lucas F, Michaels PD, Wang D, Kim AS. 2020. Mutational analysis of hematologic neoplasms in 164 paired peripheral blood and bone marrow samples by next-generation sequencing. Blood Adv. 4:4362–65
     [Google Scholar]
  193. 193.
    Sahoo SS, Pastor VB, Goodings C, Voss RK, Kozyra EJ et al. 2021. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nat. Med. 27:1806–17
     [Google Scholar]
  194. 194.
    Dawoud AAZ, Gilbert RD, Tapper WJ, Cross NCP. 2022. Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease. Leukemia 36:507–15
     [Google Scholar]
  195. 195.
    Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Arango Ossa JE et al. 2022. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evidence 1:7 https://doi.org/10.1056/EVIDoa2200008
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-pathmechdis-051222-122724
Loading
Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy
Annual Review of Pathology: Mechanisms of Disease 19, 479 (2024); https://doi.org/10.1146/annurev-pathmechdis-051222-122724
/content/journals/10.1146/annurev-pathmechdis-051222-122724
/content/journals/10.1146/annurev-pathmechdis-051222-122724
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error