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4 months ago

#leusm #DDR_pathway #TP53 #PPM1D #CHEK2 Not all DNA damage response mutations are created equal: TP53 carries the worst prognosis (master executor for leukemogenesis) PPM1D (feedback brake: Partially phenocopies TP53 but without genomic chaos) : hallmark therapy-related mutation: strongly selected by platinum and topoisomerase II inhibitors, with intermediate prognosis better than TP53m CHEK2 is unique as a germline, familial weakest leukemia driver; autosomal dominant loss-of-function variants cause earlier-onset AML/MDS with familial clustering. All three are CHIP drivers shaped by prior therapy; TP53 and PPM1D clones expand aggressively after chemo-XRT; while CHEK2 contributes modestly 👇🏽

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