Comparative outcome and prognostic factor analysis among MDS/AML patients with TP53 mutations, snps, and wild type

While variant TP53 is an adverse prognosis factor in myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), current clinical prognosis and variation feature analysis of TP53 alterations remain limited. We evaluated 333 MDS/AML patients with TP53 mutations, single nucleotide polymorphisms (SNPs), and wild-type TP53 to characterize clinical features and identify prognostic factors using next-generation sequencing (NGS) data. Interpretation requires caution due to sample size limitations, particularly in subgroup analyses. Multivariate analysis identified age, gender, cytogenetic risk, transplantation, white blood cell (WBC) count, TP53 status, and TP53 variant allele frequency (VAF) > 40% as independent prognostic factors. Patients with TP53 mutations (n = 45) had significantly worse overall survival (OS) and disease-free survival (DFS) (2-year OS: 34.94%; DFS: 38.26%) compared to those with TP53 SNPs (n = 84; 2-year OS: 77.25%; DFS: 87.54%; P < 0.001) and TP53 wild-type patients (n = 204; 2-year OS: 63.25%; DFS: 70.72%; P < 0.05). Notably, TP53 SNP carriers exhibited comparable or superior survival to TP53 wild-type patients. Focusing on the TP53 mutated cases, we identified TET2 as a possible disadvantageous prognosis factor among the coexistent gene mutations of TP53, suggesting that a potential dual-gene (TET2-TP53) mutation signature is associated with shorter survival. Therapeutic analysis revealed that transplantation improved survival in TP53 variant patients compared to chemotherapy alone, supporting its role as an effective intervention. Our findings highlight the prognostic significance of TP53 alterations in MDS/AML and underscore the importance of karyotype risk stratification, post-transplant relapse prevention, and mutation monitoring to optimize outcomes. Future studies with larger cohorts are needed to validate these results.