Clinical Lymphoma, Myeloma & Leukemia, Vol.23, Suppl.1 - September 2023

S74 and incidence of hematologic malignancy.29 Given survival data in CHIP/CCUS,7,30 prospective evaluation interventions that mitigate the risk of CVD outcomes in CHIP/CCUS may prove more impactful at a population level. As patients with CHIP/CCUS are asymptomatic, ideal interventions will change clonal trajectories and prevent adverse outcomes with minimal toxicity. Translational research using patient-derived models of CHIP/CCUS to identify novel therapeutic targets and safe and effective therapies will be critical to the advancement of this field. References 1. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/ Dendritic Neoplasms. Leukemia. 2022. 2. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488-2498. 3. Genovese G, Jaiswal S, Ebert BL, McCarroll SA. Clonal hematopoiesis and blood-cancer risk. N Engl J Med. 2015;372(11):1071-1072. 4. Xie M, Lu C, Wang J, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472-1478. 5. McKerrell T, Park N, Moreno T, et al. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 2015;10(8):1239-1245. 6. Genovese G, Kähler AK, Handsaker RE, et al. Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. New England Journal of Medicine. 2014;371(26):2477-2487. 7. Jaiswal S, Natarajan P, Silver AJ, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017;377(2):111-121. 8. Coombs CC, Zehir A, Devlin SM, et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell. 2017;21(3):374-382.e374. 9. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer Journal for Clinicians. 2022;72(1):7-33. 10. Fabre MA, de Almeida JG, Fiorillo E, et al. The longitudinal dynamics and natural history of clonal haematopoiesis. Nature. 2022;606(7913):335-342. 11. Hsu JI, Dayaram T, Tovy A, et al. PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy. Cell Stem Cell. 2018;23(5):700-713.e706. 12. Bolton KL, Ptashkin RN, Gao T, et al. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat Genet. 2020;52(11):1219-1226. 13. Weeks LD, Niroula A, Neuberg D, et al. Prediction of Risk for Myeloid Malignancy in Clonal Hematopoiesis. NEJM Evidence. 2023;2(5):EVIDoa2200310. 14. Busque L, Patel JP, Figueroa ME, et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nature Genetics. 2012;44(11):1179-1181. 15. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):916. 16. Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017;17(1):5-19. 17. Zink F, Stacey SN, Norddahl GL, et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood. 2017;130(6):742-752. 18. Vlasschaert C, Mack T, Heimlich JB, et al. A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets. Blood. 2023;141(18):2214-2223. 19. Niroula A, Sekar A, Murakami MA, et al. Distinction of lymphoid and myeloid clonal hematopoiesis. Nat Med. 2021;27(11):1921-1927. 20. Buscarlet M, Provost S, Zada YF, et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood. 2017;130(6):753-762. 21. Gibson CJ, Lindsley RC, Tchekmedyian V, et al. Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma. J Clin Oncol. 2017;35(14):1598-1605. 22. Levin MG, Nakao T, Zekavat SM, et al. Genetics of smoking and risk of clonal hematopoiesis. Sci Rep. 2022;12(1):7248. 23. Dawoud AAZ, Tapper WJ, Cross NCP. Clonal myelopoiesis in the UK Biobank cohort: ASXL1 mutations are strongly associated with smoking. Leukemia. 2020;34(10):2660-2672. 24. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559(7714):400-404. 25. Gao T, Ptashkin R, Bolton KL, et al. Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis. Nat Commun. 2021;12(1):338. 26. Malcovati L, Gallì A, Travaglino E, et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood. 2017;129(25):3371-3378. 27. Steensma DP, Bolton KL. What to tell your patient with clonal hematopoiesis and why: insights from 2 specialized clinics. Blood. 2020;136(14):1623-1631. 28. Bolton KL, Zehir A, Ptashkin RN, et al. The Clinical Management of Clonal Hematopoiesis: Creation of a Clonal Hematopoiesis Clinic. Hematol Oncol Clin North Am. 2020;34(2):357-367. 29. Xie Z, DeZern AE. How Great Is the Threat of Clonal Hematopoiesis? Let This New Risk Score Be Your Guide. NEJM Evidence. 2023;2(5):EVIDe2300053. 30. Gumuser Esra D, Schuermans A, Cho So Mi J, et al. Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease. Journal of the American College of Cardiology. 2023;81(20):1996-2009.

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