Mutation Profile Of Ppm1d And Tp53 In Patients With Myelodysplastic Syndromes And Complex Chromosome Abnormalities

Introduction: Complex (≥3) abnormalities (cA) are associated with an inferior outcome in myelodysplastic syndromes (MDS). About 50% of MDS with cA show mutations in TP53 that might contribute to the formation of the cA and worsen prognosis (Haase et al., Leukemia, 2019). In former single nucleotid polymorphism (SNP) analysis we found chromosome 17q being affected in several patients with cA with a higher incidence as by chance. In just this region is a gene called PPM1D located which already has been observed as one of the most frequently mutated genes in pts./individuals with clonal hematopoiesis with indetermined significance (CHIP). PPM1D is encoding for a protein named Wip1. This protein acts as an inhibitor of p53. About 5% of MDS with 5q deletions show mutations in PPM1D (Panagiota et al., ASH 2017). Mutations in PPM1D are even more common among pts with therapy-related MDS (15%, Lindsley et al., 2017). The aim of our study was to determine the frequency of PPM1D mutations in MDS with cA and to shed light upon their possible contribution to the formation of cA.