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Clonal hematopoiesis and hematological malignancy
William G. Dunn, … , Matthew A. McLoughlin, George S. Vassiliou
William G. Dunn, … , Matthew A. McLoughlin, George S. Vassiliou
Published October 1, 2024
Citation Information: J Clin Invest. 2024;134(19):e180065. https://doi.org/10.1172/JCI180065.
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Review Series

Clonal hematopoiesis and hematological malignancy

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Abstract

Clonal hematopoiesis (CH), the expansion of hematopoietic stem cells and their progeny driven by somatic mutations in leukemia-associated genes, is a common phenomenon that rises in prevalence with advancing age to affect most people older than 70 years. CH remains subclinical in most carriers, but, in a minority, it progresses to a myeloid neoplasm, such as acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm. Over the last decade, advances in our understanding of CH, its molecular landscape, and the risks associated with different driver gene mutations have culminated in recent developments that allow for a more precise estimation of myeloid neoplasia risk in CH carriers. In turn, this is leading to the development of translational and clinical programs to intercept and prevent CH from developing into myeloid neoplasia. Here, we give an overview of the spectrum of CH driver mutations, what is known about their pathophysiology, and how this informs the risk of incident myeloid malignancy.

Authors

William G. Dunn, Matthew A. McLoughlin, George S. Vassiliou

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Figure 3

Risk stratification of CH.

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Risk stratification of CH.
A hypothetical individual with DNMT3A and IDH...
A hypothetical individual with DNMT3A and IDH2-mutated CH is used as an exemplar. NGS, demographic, and complete blood count data are used as inputs into two CH risk stratification tools (144,148), and both identify the individual as being at high risk of incident MN. The clonal hematopoiesis risk score (CHRS) (148) (available online at http://www.chrsapp.com/) designates the individual as “high risk” and depicts the cumulative incidence of myeloid neoplasia for this subset. The output of MN-predict (144) (available online at https://bioinf.stemcells.cam.ac.uk/shiny/vassiliou/MN_predict) shows the probability of progression to each MN subtype, highlighting that the risk is predominantly related to transformation to AML in this sample case. Images from CHRS and MN-predict tools were reproduced with permission. Hb, hemoglobin; MCV, mean corpuscular volume; PLT, platelet count; RDW, red cell distribution width.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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