TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Current Guidelines, Therapies, and Future Considerations

Abstract

<b><i>Background:</i></b> Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene <i>TP53</i> plays a crucial role in maintaining genomic integrity and preventing the development of cancer. <i>TP53</i> mutations are frequently observed in AML (∼10% of patients) and are associated with aggressive disease behavior, resistance to therapy, and poor prognosis. <b><i>Summary:</i></b> Recent changes in classification of <i>TP53</i>-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of <i>TP53</i> and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/− venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of <i>TP53</i>-mutated MDS/AML have focused on immunotherapies. <b><i>Key Messages:</i></b> Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of <i>TP53</i>-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy.