GRCh38 · COSMIC v99


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Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential.
Paper ID
Wong TN, Miller CA, Jotte MRM, Bagegni N, Baty JD, Schmidt AP, Cashen AF, Duncavage EJ, Helton NM, Fiala M, Fulton RS, Heath SE, Janke M, Luber K, Westervelt P, Vij R, DiPersio JF, Welch JS, Graubert TA, Walter MJ, Ley TJ and Link DC
Division of Oncology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nature communications, 2018;9(1):455
ISSN: 2041-1723
PMID: 29386642 (view at PubMed or Europe PMC)
Hematopoietic clones harboring specific mutations may expand over time. However, it remains unclear how different cellular stressors influence this expansion. Here we characterize clonal hematopoiesis after two different cellular stressors: cytotoxic therapy and hematopoietic transplantation. Cytotoxic therapy results in the expansion of clones carrying mutations in DNA damage response genes, including TP53 and PPM1D. Analyses of sorted populations show that these clones are typically multilineage and myeloid-biased. Following autologous transplantation, most clones persist with stable chimerism. However, DNMT3A mutant clones often expand, while PPM1D mutant clones often decrease in size. To assess the leukemic potential of these expanded clones, we genotyped 134 t-AML/t-MDS samples. Mutations in non-TP53 DNA damage response genes are infrequent in t-AML/t-MDS despite several being commonly identified after cytotoxic therapy. These data suggest that different hematopoietic stressors promote the expansion of distinct long-lived clones, carrying specific mutations, whose leukemic potential depends partially on the mutations they harbor.
Paper Status