Abstract
TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain a challenging spectrum of clonal myeloid disease with poor prognosis. Recent studies have shown that in AML, MDS, and MDS/AML with biallelic TP53 loss, the TP53-mutated clone becomes dominant. These are highly aggressive diseases that are resistant to most chemotherapies. The latest 2022 International Consensus Classification categorizes these diseases under “myeloid disease with mutated TP53.” All treatment approaches have not improved survival rates for this disease. Many newer therapies are on the horizon, including chimeric antigen receptor T/NK-cell therapies, mutated p53 reactivators, Fc fusion protein, and monoclonal antibodies targeting various myeloid antigens. This review summarizes the current approaches for myeloid disease with TP53 mutation and provides an overview of emerging nontransplant approaches.