Navigating prognostic stratification and approach to TP53-mutated myeloid neoplasms

Abstract

Purpose of review – TP53-mutated (TP53-MT) myeloid neoplasms (MN) represent one of the most challenging disease subsets due to their distinct pathobiology, frequent association with therapy-related disease, chemo-resistant phenotype, and dismal outcomes. The prognostic impact of TP53-MT is not uniform and is influenced by disease state, allelic burden, and co-occurring cytogenetic and molecular aberrations that shape disease trajectory. While current prognostic models incorporate TP53 status, they incompletely capture the heterogeneity within TP53-MT MN. Therapeutic options remain limited, with allogeneic stem cell transplantation being the only intervention offering long-term survival in selected patients. Recent findings – Novel approaches, including p53 reactivators and anti-CD47 antibodies in combination with standard-of-care therapies, have been explored; however, none has yet transformed the natural history of TP53-MT MN. Summary – This review highlights the current understanding of TP53-MT MN, evolving strategies of prognostic stratification and propose a practical framework for clinical management. We further discuss the critical unmet need for collaborative, biologically informed clinical trials to improve outcomes of this challenging disease entity.