CHIPing out PPM1D-mutant hematopoiesis

摘要

Deep sequencing approaches have allowed researchers to identify a wide spectrum of somatic mutations in hematopoietic cells (HSCs) of individuals without a known hematologic disorder. Recurrent variants in protein phosphatase Mg21/Mn21 1D (PPM1D), a serine/threonine phosphatase involved in the regulation of DNA damage response (DDR), were found to be highly enriched in blood cells of cancer patients previously treated with cytotoxic agents. 1,2 In this issue of Blood, Kahn et al provide evidence on how PPM1D mutations confer a selective growth advantage in the presence of ongoing DNA damage and demonstrate that pharmacological targeting of PPM1D is able to reverse this effect.(3)