الفهرس 
ContentsOnly 14 pages are availabe for public view
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Abstract
The size of PPM1D-mutated clones is relatively small compared to that of clones with other mutations in myeloid neoplasms. All PPM1D mutations were heterozygous and mutually exclusive with TP53 somatic mutations. All PPM1D mutations were found only in therapy related myelodysplastic syndrome (t-MDS) / acute myeloid leukemia (t-AML). Clearly, TP53 and PPM1D mutations are enriched in t-MDS due to direct therapy-related effects. TP53 GL mutations are related to GL-encoded cancer predisposition. Unlike TP53, PPM1D was not significantly associated with complex cytogenetics or deletions. TP53 and PPM1D mutations are functionally related and share a similar spectrum of myeloid neoplasms including MDS and t-MDS and t-AML. PPM1D mutations and high PPM1D expression are involved in the pathogenesis of myeloid neoplasms. While TP53 hits occur as ancestral and secondary hits in a spontaneous MDS/AML with unexpectedly significant proportion of GL variants. In contrast, PPM1D mutations are somatic, exclusively present in t-MN and are mutually exclusive with TP53 mutations. Clearly, TP53 and PPM1D mutations are enriched in t-MDS due to direct therapy-related effects. TP53 GL mutations are related to GL-encoded cancer predisposition. In first scenario, chemotherapy might cause acquisition of second hit, while it is also possible that preexisting tiny clones with biallelic TP53 mutations are being selected for chemotherapy. PPM1D mutations and high PPM1D expression are involved in the pathogenesis of myeloid neoplasms. TP53 hits occur as ancestral and secondary hits in a spontaneous MDS/AML with unexpectedly significant proportion of GL variants. PPM1D mutations are somatic, exclusively present in t-MN and are mutually exclusive with TP53 mutations. Regarding our study, PPM1D mutations have no effect on the survival of t-MN. TP53 and PPM1D mutations are enriched in t-MDS, likely because chemotherapy exerts systemic selective pressure for the apoptotic resistant cells. PPM1D gene expression studies are required to accurately detect the role of the mutant PPM1D in the pathogenesis of t-MN. Designing inhibitors for mutant PPM1D and/or P53 could be new tools of targeted therapy in patients with myeloid neoplasms.