Clonal Hematopoiesis in Hematologic Malignancies, Bone Marrow Failure Syndromes, and Stem Cell Clones – Cancer Therapy Advisor

Clonal hematopoiesis (CH) occurs when a large fraction of mature blood cells originate from a single hematopoietic stem cell, and is more commonly seen within aging populations. Current evidence suggests somatic mutations in candidate driver genes are responsible for some cases. CH of indeterminate potential, or CHIP, describes CH that co-occurs with a mutation in a leukemia-associated gene at a variant allele frequency of 0.02 or higher, and is associated with an increased risk for myocardial infarction, ischemic stroke, and all-cause mortality.1,2 Recent studies have established an association between CH and hematologic malignancies.3,4

In a review article published in Blood, Julia T. Warren, MD, PhD, and Daniel C. Link, MD, both from the division of hematology-oncology at Washington University School of Medicine in St. Louis, Missouri, summarized current literature investigating the association between CH and hematopoietic malignancy. In addition, they examined aspects of CH associated with leukemic progression.3

CH and Risk for Hematologic Malignancy

CH attributable to point mutations are associated with nearly a 10-fold higher risk of hematopoietic malignancy. While the absolute risk is low, specific elements of CH may result in a greater risk of progression, including the presence of multiple mutations, altered red blood indices, the presence of TP53 or splicesome gene mutations, and a variant allele fraction higher than 10%. Close monitoring is required in the setting of peripheral blood cytopenias as CH confers a high risk of transformation to a myeloid malignancy.3

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Recent evidence suggests that hematopoietic stressors, such