Characteristics and prognostic implications of <i>TP53</i> mutations in Chinese patients with myelodysplastic syndromes

Tumour protein p53 (TP53) mutations occur frequently in myelodysplastic syndromes (MDS) and are associated with a high risk of treatment failure and adverse outcomes. In this study, we analysed 1219 patients with MDS, focusing on the clinical and molecular characteristics of those with TP53 mutations and investigating factors contributing to worse survival and disease progression. One hundred and fifteen (9.4%) patients carried TP53 alterations, of which 70.4% had biallelic and 29.6% had monoallelic alterations. Individuals with biallelic mutations showed elevated bone marrow (BM) blasts (p < 0.001), decreased platelet counts (p = 0.007) and higher the Revised International Prognostic Scoring System (IPSS-R) and Molecular International Prognostic Scoring System (IPSS-M) categories. The biallelic variants, complex karyotype, -7, del(7q) and higher BM blast were linked to worse survival and a higher risk of acute myeloid leukaemia (AML) transformation in TP53-mutated patients. SF3B1 mutations were protective factors for both end-points within TP53-mutated MDS. These characteristics are very similar to populations from the International Working Group for the Prognosis of MDS (IWG-PM) cohort. By performing longitudinal sequencing, we revealed the acquisition or clonal amplification of TP53 alterations during AML transformation. We also conducted repeated sequencing in patients who achieved complete remission (CR) and observed that TP53 mutations were undetectable in 10 of 12 patients. Our findings revealed the clinical significance of TP53 mutations in MDS and highlighted the importance of early detection and dynamic monitoring of TP53 during treatment.