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Factors associated with clonal hematopoiesis and interaction with marrow environment

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Abstract

Clonal hematopoiesis (CH) is an expansion of clones in individuals without any hematologic abnormalities, often carrying the driver mutations implicated in myeloid tumors, such as DNMT3A, TET2, and ASXL1. Most notably, CH is an age-related event, accounting for ~ 10% of cases in people over 60 years old. CH may also be correlated with a previous history of cancer treatment with chemotherapeutic drugs/radiation and infection episodes. The link between aging and CH acquisition is best explained by the enhanced inflammatory level in the bone marrow environment, which in turn expands hematopoietic cell clones with mutations in myeloid drivers. This positive feedback accounts for not only increased incidence of subsequent myeloid tumors in CH carriers but also for increased all-cause mortality and cardiovascular diseases (CVD). Recent evidence from large-scale epidemiological studies with genetic profiles, and mice models that recapitulate hematopoietic clones harboring driver gene mutations has revealed the detailed pathophysiology of CH clones represented by specific driver mutations, especially regarding expansion mechanisms under environmental factors and how they alter the environment. This review introduces the current knowledge of CH with a special focus on its interaction with the marrow environment.

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Acknowledgements

This work was supported by the Japan Agency for Medical Research and Development (AMED) (JP19ck0106353h0003 to Y.N.) and KAKENHI (JP18H02836 to Y.N.).

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  1. Division of Hematopoietic Disease Control, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yasuhito Nannya

  2. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan

    Yasuhito Nannya

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Correspondence to Yasuhito Nannya.

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Nannya, Y. Factors associated with clonal hematopoiesis and interaction with marrow environment. J Bone Miner Metab 41, 380–387 (2023). https://doi.org/10.1007/s00774-022-01380-0

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