Curing the Incurable: TP53 Mutated Myeloid Neoplasms

The TP53 gene ensures genetic fidelity by regulating cell cycle kinetics and apoptosis. In myeloid neoplasms, TP53 mutation is witnessed in 13% of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Alterations in TP53 or its respective protein is associated with a near-universal dismal prognosis, especially if there is TP53 protein hyper-expression or multi-hit genetic disease as defined by: biallelic loss, 17p chromosomal deletion, complex karyotypic features, loss of heterozygosity, or variant allele frequency (VAF) of 50% or more. TP53 mutations or protein hyper-expression instill an immunosuppressive bone marrow microenvironment, exacerbating an already poor prognosis. We will survey the pathobiology of TP53 mutated/hyper-expressed myeloid disease, its classification schema, and its immunologic ramifications to the bone marrow milieu. The differential prognosis of the mutation in various chromosomal and VAF settings will be explored. Lastly, we will outline therapeutic options, promising treatments on the horizon, and whether allogeneic stem cell transplant is curative.