Among 4,905 patients screened, 133 (2.71%) carried PPM1D mutations as clonal hematopoiesis (122 analytic; 26.2% solid tumor, 73.8% hematologic). Variants were predominantly truncating. Chemotherapy-exposed hematologic patients showed higher co-mutation burden (3.0 vs 1.0, p=0.008) and more additional somatic mutations (83.7% vs 61.0%, p=0.018); ≥2 PPM1D mutations tracked with higher VAF (4.6% vs 2.9%, p=0.004), supporting therapy-driven clonal evolution.

Keywords: PPM1D, therapy-related myeloid neoplasm, clonal hematopoiesis, co-mutation burden, clonal evolution, TP53