russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2023-5511GRCBFNrussjcardiol-5511Research ArticleГЕНЕТИКА В КАРДИОЛОГИИ. ОБЗОРЫ ЛИТЕРАТУРЫVGENETICS IN CARDIOLOGY. LITERATURE REVIEWSОбщее в атеро и канцерогенезе: клональный гемопоэзCommon in atherogenesis and carcinogenesis: clonal hematopoiesishttps://orcid.org/0000-0003-3226-1750СлепцовА. А.SleptsovA. A.

Слепцов Алексей Анатольевич — кандидат медицинских наук, научный сотрудник лаборатории популяционной генетики

Томск

Tomsk

alexei.sleptcov@medgenetics.ruhttps://orcid.org/0000-0002-0673-4094НазаренкоМ. С.NazarenkoM. S.

Назаренко Мария Сергеевна — доктор медицинских наук, руководитель лаборатории популяционной генетики

Томск

Tomsk

maria.nazarenko@medgenetics.ruhttps://orcid.org/0000-0002-2113-4556ПузыревВ. П.PuzyrevV. Р.

Пузырев Валерий Павлович — доктор медицинских наук, профессор, академик РАН

Томск

Tomsk

p.valery@medgenetics.ruФГБНУ Томский национальный исследовательский медицинский центр РАН, Научно-исследовательский институт медицинской генетикиРоссияTomsk National Research Medical Center, Research Institute of Medical GeneticsRussian Federation202317072023281055115511Copyright © Слепцов А.А., Назаренко М.С., Пузырев В.П., 20232023Слепцов А.А., Назаренко М.С., Пузырев В.П.Sleptsov A.A., Nazarenko M.S., Puzyrev V.Р.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/5511

Клональный гемопоэз (КГ) — распространенное возраст-зависимое состояние, сопровождающееся экспансией мутантных гемопоэтических стволовых клеток, как результат соматических мутаций, связанное с высоким риском сердечно-сосудистых осложнений и новообразований кроветворной ткани. КГ имеет латентное течение и к 70 годам доля мутантных клонов может уже составлять >2% от общего пула циркулирующих ядросодержащих клеток крови. Ввиду непостоянства темпов накопления мутантных клонов признаки КГ могут наблюдаться и в более молодом возрасте. В целом КГ может выступать как факультативное предраковое состояние, так и как фактор риска острых сердечно-сосудистых событий атеросклеротического происхождения, таких как острый инфаркт миокарда и инсульт. Современные данные указывают, что соматические мутации в «драйверных» генах КГ значительно повышают риск таких ранее считавшихся не связанных острых состояний, как острый миелоидный лейкоз и острый инфаркт миокарда. Высокая смертность и широкая распространенность сердечно-сосудистых и онкологических заболеваний, и их сильная ассоциация с КГ с неопределенным потенциалом, делает последнее состояние объектом пристального изучения.

Clonal hematopoiesis is a common age-dependent state accompanied by the expansion of mutant hematopoietic stem cells as a result of somatic mutations and is associated with a high risk of hematopoietic neoplasms and cardiovascular diseases. Clonal hematopoiesis in human ontogenesis occurs asymptomatically, and the fraction of mutant clones can exceed more than 2% of the total pool of circulating nucleated blood cells by age 70. Due to the variability of the accumulation rate of mutant clones, signs of clonal hematopoiesis can be observed at a younger age. Clonal hematopoiesis may act as a benign, precancerous condition and a strong factor for acute cardiovascular events such as myocardial infarction and stroke. Current evidence indicates that somatic mutations in driver genes of clonal hematopoiesis significantly increase the risk of acute conditions such as acute myeloid leukemia and acute myocardial infarction. The high mortality and morbidity of cardiovascular and cancer diseases, and their strong association with clonal hematopoiesis, make it of indeterminate potential worthy of close attention.

клональный гемопоэзатеросклерозсердечно-сосудистое заболеваниеклональный гемопоэз с неопределенным потенциаломгенетическая гетерогенностьлокусная гетерогенностьострый миелоидный лейкозclonal hematopoiesisatherosclerosiscardiovascular diseaseclonal hematopoiesis of indeterminate potentialgenetic heterogeneitylocus heterogeneityacute myeloid leukemiaИсследование поддержано грантом Российского научного фонда № 22-25-00745The study was supported by the Russian Science Foundation grant № 22-25-00745ReferencesSawai CM, Babovic S, Upadhaya S, et al. Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals. Immunity. 2016;45:597-609. doi:10.1016/j.immuni.2016.08.007.Sawai CM, Babovic S, Upadhaya S, et al. Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals. Immunity. 2016;45:597-609. doi:10.1016/j.immuni.2016.08.007.Lee-Six H, Øbro NF, Shepherd MS, et al. Population dynamics of normal human blood inferred from somatic mutations. Nature. 2018;561:473-8. doi:10.1038/s41586-018-0497-0.Lee-Six H, Øbro NF, Shepherd MS, et al. Population dynamics of normal human blood inferred from somatic mutations. Nature. 2018;561:473-8. doi:10.1038/s41586-018-0497-0.Sun J, Ramos A, Chapman B, et al. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322-7. doi:10.1038/nature13824.Sun J, Ramos A, Chapman B, et al. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322-7. doi:10.1038/nature13824.Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nature Reviews Molecular Cell Biology. 2019;20:303-20. doi:10.1038/s41580-019-0103-9.Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nature Reviews Molecular Cell Biology. 2019;20:303-20. doi:10.1038/s41580-019-0103-9.Bellinger DL, Lorton D, Felten SY, et al. Innervation of lymphoid organs and implications in development aging, and autoimmunity. International Journal of Immunopharmacology. 1992;14:329-44. doi:10.1016/0192-0561(92)90162-e.Bellinger DL, Lorton D, Felten SY, et al. Innervation of lymphoid organs and implications in development aging, and autoimmunity. International Journal of Immunopharmacology. 1992;14:329-44. doi:10.1016/0192-0561(92)90162-e.Beerman I, Bock C, Garrison BS, et al. Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging. Cell Stem Cell. 2013;12:413-25. doi:10.1016/j.stem.2013.01.017.Beerman I, Bock C, Garrison BS, et al. Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging. Cell Stem Cell. 2013;12:413-25. doi:10.1016/j.stem.2013.01.017.Welch JS, Ley TJ, Link DC, et al. The Origin and Evolution of Mutations in Acute Myeloid Leukemia. Cell. 2012;150:264-78. doi:10.1016/j.cell.2012.06.023.Welch JS, Ley TJ, Link DC, et al. The Origin and Evolution of Mutations in Acute Myeloid Leukemia. Cell. 2012;150:264-78. doi:10.1016/j.cell.2012.06.023.Bick AG, Weinstock JS, Nandakumar SK, et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature. 2020;586:763-8. doi:10.1038/s41586-020-2819-2.Bick AG, Weinstock JS, Nandakumar SK, et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature. 2020;586:763-8. doi:10.1038/s41586-020-2819-2.Zink F, Stacey SN, Norddahl GL, et al. K.Clonal hematopoiesis with and without candidate driver mutations, is common in the elderly. Blood. 2017;130:742-52. doi:10.1182/blood2017-02-769869.Zink F, Stacey SN, Norddahl GL, et al. K.Clonal hematopoiesis with and without candidate driver mutations, is common in the elderly. Blood. 2017;130:742-52. doi:10.1182/blood2017-02-769869.Heyde A, Rohde D, McAlpine CS, et al. Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell. 2021;184:1348-61.e22. doi:10.1016/j.cell.2021.01.049.Heyde A, Rohde D, McAlpine CS, et al. Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell. 2021;184:1348-61.e22. doi:10.1016/j.cell.2021.01.049.Geiger H, de Haan G, Florian MC. The ageing haematopoietic stem cell compartment. Nature Reviews Immunology. 2013;13:376-89. doi:10.1038/nri3433.Geiger H, de Haan G, Florian MC. The ageing haematopoietic stem cell compartment. Nature Reviews Immunology. 2013;13:376-89. doi:10.1038/nri3433.Linton PJ, Dorshkind K.Age-related changes in lymphocyte development and function. Nature Immunology. 2004;5:133-9. doi:10.1038/ni1033.Linton PJ, Dorshkind K.Age-related changes in lymphocyte development and function. Nature Immunology. 2004;5:133-9. doi:10.1038/ni1033.Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263-8. doi:10.1182/blood-2004-05-1812.Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263-8. doi:10.1182/blood-2004-05-1812.Yamamoto R, Wilkinson AC, Ooehara J, et al. Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment. Cell Stem Cell. 2018;22:600-7.e4. doi:10.1016/j.stem.2018.03.013.Yamamoto R, Wilkinson AC, Ooehara J, et al. Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment. Cell Stem Cell. 2018;22:600-7.e4. doi:10.1016/j.stem.2018.03.013.Holstege H, Pfeiffer W, Sie D, et al. Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis. Genome Res. 2014;24:733-42. doi:10.1101/gr.162131.113.Holstege H, Pfeiffer W, Sie D, et al. Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis. Genome Res. 2014;24:733-42. doi:10.1101/gr.162131.113.d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426:194-8. doi:10.1038/nature02118.d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426:194-8. doi:10.1038/nature02118.Wang J, Lu X, Sakk V, et al. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood. 2014;124:3237-40. doi:10.1182/blood-2014-04-568055.Wang J, Lu X, Sakk V, et al. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood. 2014;124:3237-40. doi:10.1182/blood-2014-04-568055.Young AL, Challen GA, Birmann BM, et al. Clonal haematopoiesis harbouring AMLassociated mutations is ubiquitous in healthy adults. Nat Commun. 2016;7:12484. doi:10.1038/ncomms12484.Young AL, Challen GA, Birmann BM, et al. Clonal haematopoiesis harbouring AMLassociated mutations is ubiquitous in healthy adults. Nat Commun. 2016;7:12484. doi:10.1038/ncomms12484.Shlush LI. Age-related clonal hematopoiesis. Blood. 2018;131:496-504. doi:10.1182/blood-2017-07-746453.Shlush LI. Age-related clonal hematopoiesis. Blood. 2018;131:496-504. doi:10.1182/blood-2017-07-746453.Steensma DP. Clinical Implications of Clonal Hematopoiesis. Mayo Clinic Proceedings. 2018;93:1122-30. doi:10.1016/j.mayocp.2018.04.002.Steensma DP. Clinical Implications of Clonal Hematopoiesis. Mayo Clinic Proceedings. 2018;93:1122-30. doi:10.1016/j.mayocp.2018.04.002.Brojakowska A, Kour A, Thel MC, et al. Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts. Commun Biol. 2022;5:828. doi:10.1038/s42003-022-03777-z.Brojakowska A, Kour A, Thel MC, et al. Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts. Commun Biol. 2022;5:828. doi:10.1038/s42003-022-03777-z.Mencia-Trinchant N, MacKay MJ, Chin C, et al. Clonal Hematopoiesis Before, During, and After Human Spaceflight. Cell Rep. 2020;33:108458. doi:10.1016/j.celrep.2020.108458.Mencia-Trinchant N, MacKay MJ, Chin C, et al. Clonal Hematopoiesis Before, During, and After Human Spaceflight. Cell Rep. 2020;33:108458. doi:10.1016/j.celrep.2020.108458.Kar SP, Quiros PM, Gu M, et al. Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis. Nat Genet. 2022;54:1155-66. doi:10.1038/s41588-022-01121-z.Kar SP, Quiros PM, Gu M, et al. Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis. Nat Genet. 2022;54:1155-66. doi:10.1038/s41588-022-01121-z.Duncavage EJ, Tandon B.The utility of next-generation sequencing in diagnosis and monitoring of acute myeloid leukemia and myelodysplastic syndromes. International Journal of Laboratory Hematology. 2015;37:115-21. doi:10.1111/ijlh.12361.Duncavage EJ, Tandon B.The utility of next-generation sequencing in diagnosis and monitoring of acute myeloid leukemia and myelodysplastic syndromes. International Journal of Laboratory Hematology. 2015;37:115-21. doi:10.1111/ijlh.12361.Razavi P, Li BT, Brown DN, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25:1928-37. doi:10.1038/s41591-019-0652-7.Razavi P, Li BT, Brown DN, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25:1928-37. doi:10.1038/s41591-019-0652-7.Silver AJ, Jaiswal S. Clonal hematopoiesis: Pre-cancer PLUS. Advances in Cancer Research. 2019;141:85-128. doi:10.1016/bs.acr.2018.12.003.Silver AJ, Jaiswal S. Clonal hematopoiesis: Pre-cancer PLUS. Advances in Cancer Research. 2019;141:85-128. doi:10.1016/bs.acr.2018.12.003.Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9-16. doi:10.1182/blood-2015-03-631747.Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9-16. doi:10.1182/blood-2015-03-631747.Loh P-R, Genovese G, Handsaker RE, et al. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature. 2018;559:350-5. doi:10.1038/s41586-018-0321-x.Loh P-R, Genovese G, Handsaker RE, et al. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature. 2018;559:350-5. doi:10.1038/s41586-018-0321-x.Björkegren JLM, Lusis AJ. Atherosclerosis: Recent developments. Cell. 2022;185:1630-45. doi:10.1016/j.cell.2022.04.004.Björkegren JLM, Lusis AJ. Atherosclerosis: Recent developments. Cell. 2022;185:1630-45. doi:10.1016/j.cell.2022.04.004.Desai P, Mencia-Trinchant N, Savenkov O, et al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nature Medicine. 2018;24:1015-23. doi:10.1038/s41591-018-0081-z.Desai P, Mencia-Trinchant N, Savenkov O, et al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nature Medicine. 2018;24:1015-23. doi:10.1038/s41591-018-0081-z.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;371:2477-87. doi:10.1056/nejmoa1409405.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;371:2477-87. doi:10.1056/nejmoa1409405.Jaiswal S, Fontanillas P, Flannick J, et al. Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. New England Journal of Medicine. 2014;371:2488-98. doi:10.1056/nejmoa1408617.Jaiswal S, Fontanillas P, Flannick J, et al. Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. New England Journal of Medicine. 2014;371:2488-98. doi:10.1056/nejmoa1408617.Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559:400-4. doi:10.1038/s41586-018-0317-6.Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559:400-4. doi:10.1038/s41586-018-0317-6.Tefferi A, Pardanani A.Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncology. 2015;1:97-105. doi:10.1001/jamaoncol.2015.89.Tefferi A, Pardanani A.Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncology. 2015;1:97-105. doi:10.1001/jamaoncol.2015.89.Hansen JW, Pedersen DA, Larsen LA, et al. Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality. Blood. 2020;135:261-8. doi:10.1182/blood.2019001793.Hansen JW, Pedersen DA, Larsen LA, et al. Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality. Blood. 2020;135:261-8. doi:10.1182/blood.2019001793.Mitchell RL, Kosche C, Burgess K, et al. Misdiagnosis of Li-Fraumeni Syndrome in a Patient With Clonal Hematopoiesis and a Somatic TP53 Mutation. Journal of the National Comprehensive Cancer Network. 2018;16:461-6. doi:10.6004/jnccn.2017.7058.Mitchell RL, Kosche C, Burgess K, et al. Misdiagnosis of Li-Fraumeni Syndrome in a Patient With Clonal Hematopoiesis and a Somatic TP53 Mutation. Journal of the National Comprehensive Cancer Network. 2018;16:461-6. doi:10.6004/jnccn.2017.7058.Cazzola M, Malcovati L. Myelodysplastic syndromes-coping with ineffective hematopoiesis. N Eng J Med. 2005;352:536-8. doi:10.1056/NEJMp048266.Cazzola M, Malcovati L. Myelodysplastic syndromes-coping with ineffective hematopoiesis. N Eng J Med. 2005;352:536-8. doi:10.1056/NEJMp048266.Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-99.Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-99.Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nature Reviews Cancer. 2016;17:5-19. doi:10.1038/nrc.2016.112.Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nature Reviews Cancer. 2016;17:5-19. doi:10.1038/nrc.2016.112.Ковригина А.М., Глинкина С.А., Байков В.В. Принципы патоморфологической дифференциальной диагностики миелодиспластических синдромов. Клиническая онкогематология. 2015;8:62-8.Kovrigina AM, Glinkina SA, Baikov VV. Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes. Klin. Onkogematol. 2015;8:62-8 (In Russ.)Ma X.Epidemiology of Myelodysplastic Syndromes. The American Journal of Medicine. 2012;125:S2-S5. doi:10.1016/j.amjmed.2012.04.014.Ma X.Epidemiology of Myelodysplastic Syndromes. The American Journal of Medicine. 2012;125:S2-S5. doi:10.1016/j.amjmed.2012.04.014.Veiga CB, Lawrence EM, Murphy AJ, et al. Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease. Cancers. 2021;13:1968. doi:10.3390/cancers13081968.Veiga CB, Lawrence EM, Murphy AJ, et al. Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease. Cancers. 2021;13:1968. doi:10.3390/cancers13081968.Cazzola M, Della Porta MG, Malcovati L.The genetic basis of myelodysplasia and its clinical relevance. Blood. 2013;122:4021-34. doi:10.1182/blood-2013-09-381665.Cazzola M, Della Porta MG, Malcovati L.The genetic basis of myelodysplasia and its clinical relevance. Blood. 2013;122:4021-34. doi:10.1182/blood-2013-09-381665.Natarajan P, Jaiswal S, Kathiresan S.Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis. Circ Genom Precis Med. 2018;11:e001926. doi:10.1161/circgen.118.001926.Natarajan P, Jaiswal S, Kathiresan S.Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis. Circ Genom Precis Med. 2018;11:e001926. doi:10.1161/circgen.118.001926.Schloss MJ, Swirski FK, Nahrendorf M.Modifiable Cardiovascular Risk Hematopoiesis, and Innate Immunity. Circulation Research. 2020;126:1242-59.Schloss MJ, Swirski FK, Nahrendorf M.Modifiable Cardiovascular Risk Hematopoiesis, and Innate Immunity. Circulation Research. 2020;126:1242-59.Jaiswal S, Natarajan P, Silver AJ, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. New England Journal of Medicine. 2017;377:111-21. doi:10.1056/nejmoa1701719.Jaiswal S, Natarajan P, Silver AJ, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. New England Journal of Medicine. 2017;377:111-21. doi:10.1056/nejmoa1701719.Fuster JJ, Walsh K.Somatic Mutations and Clonal Hematopoiesis. Circulation Research. 2018;122:523-32. doi:10.1161/circresaha.117.312115.Fuster JJ, Walsh K.Somatic Mutations and Clonal Hematopoiesis. Circulation Research. 2018;122:523-32. doi:10.1161/circresaha.117.312115.Sano S, Oshima K, Wang Y, et al. Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome. Journal of the American College of Cardiology. 2018;71:875-86. doi:10.1016/j.jacc.2017.12.037.Sano S, Oshima K, Wang Y, et al. Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome. Journal of the American College of Cardiology. 2018;71:875-86. doi:10.1016/j.jacc.2017.12.037.Wang W, Liu W, Fidler T, et al. Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice. Circulation Research. 2018;123:e35- e47. doi:10.1161/circresaha.118.313283.Wang W, Liu W, Fidler T, et al. Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice. Circulation Research. 2018;123:e35- e47. doi:10.1161/circresaha.118.313283.Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Science Translational Medicine. 2018;10:eaan8292. doi:10.1126/scitranslmed.aan8292.Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Science Translational Medicine. 2018;10:eaan8292. doi:10.1126/scitranslmed.aan8292.Dorsheimer L, Assmus B, Rasper T, et al. Association of Mutations Contributing to Clonal Hematopoiesis With Prognosis in Chronic Ischemic Heart Failure. JAMA Cardiol. 2019;4:32-40. doi:10.1001/jamacardio.2018.3965.Dorsheimer L, Assmus B, Rasper T, et al. Association of Mutations Contributing to Clonal Hematopoiesis With Prognosis in Chronic Ischemic Heart Failure. JAMA Cardiol. 2019;4:32-40. doi:10.1001/jamacardio.2018.3965.Fidler TP, Xue C, Yalcinkaya M, et al. The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature. 2021;592:296-301. doi:10.1038/s41586-021-03341-5.Fidler TP, Xue C, Yalcinkaya M, et al. The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature. 2021;592:296-301. doi:10.1038/s41586-021-03341-5.Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nature Reviews Cardiology. 2020;18:58-68. doi:10.1038/s41569-020-0431-7.Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nature Reviews Cardiology. 2020;18:58-68. doi:10.1038/s41569-020-0431-7.Bouzid H, Belk JA, Jan M, et al. Clonal hematopoiesis is associated with protection from Alzheimer’s disease. Nature Medicine. 2023. doi:10.1038/s41591-023-02397-2.Bouzid H, Belk JA, Jan M, et al. Clonal hematopoiesis is associated with protection from Alzheimer’s disease. Nature Medicine. 2023. doi:10.1038/s41591-023-02397-2.Jongen-Lavrencic M, Grob T, Hanekamp D, et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. New England Journal of Medicine. 2018;378:1189-99. doi:10.1056/nejmoa1716863.Jongen-Lavrencic M, Grob T, Hanekamp D, et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. New England Journal of Medicine. 2018;378:1189-99. doi:10.1056/nejmoa1716863.Gibson CJ, Steensma DP. New Insights from Studies of Clonal Hematopoiesis. Clinical Cancer Research. 2018;24:4633-42. doi:10.1158/1078-0432.ccr-17-3044.Gibson CJ, Steensma DP. New Insights from Studies of Clonal Hematopoiesis. Clinical Cancer Research. 2018;24:4633-42. doi:10.1158/1078-0432.ccr-17-3044.Tiacci E, Venanzi A, Ascani S, et al. High-Risk Clonal Hematopoiesis as the Origin of AITL and NPM1-Mutated AML. New England Journal of Medicine. 2018;379:981-4. doi:10.1056/nejmc1806413.Tiacci E, Venanzi A, Ascani S, et al. High-Risk Clonal Hematopoiesis as the Origin of AITL and NPM1-Mutated AML. New England Journal of Medicine. 2018;379:981-4. doi:10.1056/nejmc1806413.Hidalgo A, Tall AR. Leducq Transatlantic Network on Clonal Hematopoiesis and Atherosclerosis. Circ Res. 2019;124:481-3. doi:10.1161/CIRCRESAHA.119.314677.Hidalgo A, Tall AR. Leducq Transatlantic Network on Clonal Hematopoiesis and Atherosclerosis. Circ Res. 2019;124:481-3. doi:10.1161/CIRCRESAHA.119.314677.Nazarenko MS, Sleptcov AA, Lebedev IN, et al. Genomic structural variations for cardiovascular and metabolic comorbidity. Sci Rep. 2017;7:41268. doi:10.1038/srep41268.Nazarenko MS, Sleptcov AA, Lebedev IN, et al. Genomic structural variations for cardiovascular and metabolic comorbidity. Sci Rep. 2017;7:41268. doi:10.1038/srep41268.DiRenzo D, Owens GK, Leeper NJ. "Attack of the Clones": Commonalities Between Cancer and Atherosclerosis. Circ Res. 2017;120:624-6. doi:10.1161/CIRCRESAHA.116.310091.DiRenzo D, Owens GK, Leeper NJ. "Attack of the Clones": Commonalities Between Cancer and Atherosclerosis. Circ Res. 2017;120:624-6. doi:10.1161/CIRCRESAHA.116.310091.

The authors declare that there are no conflicts of interest present.