Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts

Abstract

Introduction Myeloid tumors typically harbor TP53 mutations, which are linked to a dismal prognosis. There are fewer studies on whether TP53‐mutated acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS‐EB) differ in molecular characteristics and should be considered as separate entities. Methods Between January 2016 and December 2021, a retrospective analysis was done on a total of 73 newly diagnosed AML patients and 61 MDS‐EB patients from the first affiliated hospital of Soochow University. We described a survival profile and a thorough characterization of newly found TP53‐mutant AML and MDS‐EB and investigated the relationship between these characteristics and overall survival (OS). Results 38 (31.1%) were mono‐allelic, and 84 (68.9%) were bi‐allelic. There is no significant difference between TP53‐mutated AML and MDS‐EB (median OS 12.9 verse 14.4 months; p = .558). Better overall survival was linked to mono‐allelic TP53 than bi‐allelic TP53(HR = 3.030, CI:1.714–5.354, p < .001). However, the number of TP53 mutations and comutations were not significantly associated with OS. TP53 variant allele frequency cutoff of 50% is significant correlation with OS (HR: 2.177, 95% CI: 1.142–4.148; p = .0063). Conclusion Our data revealed that allele status and allogeneic hematopoietic stem cell transplant independently affect the prognostic of AML and MDS‐EB patients, with a concordance of molecular features and survival between these two disease entities. Our analysis favors considering TP53‐mutated AML/MDS‐EB as a distinct disorder.