TP53-mutant myelodysplastic syndrome and acute myeloid leukemia: the black hole of hematology
Abstract
A recent article in Blood Advances by Short et al 1 entitled “ Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia, ” had very interesting conclusions that we are eager to interpret alongside our own published data on a similar topic. 2 Herein, we will summarize the fundamental problem with TP53 -mutant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), summarize the data by Short et al 1 and our own institutional data, and postulate a call to action to help motivate groups to collaborate on the issue of TP53 -mutant MDS and AML. It has been well-known for several years that TP53 aberrations are associated with exceptionally adverse outcomes for patients with MDS or AML, and there are no US Food and Drug Administration – approved targeted therapies for the subset of patients with this mutation. The fi eld of TP53 -mutant myeloid neoplasms is arguably the largest black hole in hematologic malignancies. In late 2020, the leading pharmacologic compound for treatment was eprenatapopt (APR-246), but this compound missed the primary end point in phase 3 data, leaving us with no precision approaches for TP53 -aberrant myeloid neoplasms. Transplantation is a consideration for curative-intent therapy, but because data on transplantation outcomes are a mandatory reporting requirement for the Center for International Blood and Marrow Transplant Research (CIBMTR), many centers might choose not to offer…
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