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Mutations of the tumor suppressor gene TP53 represent a common mutation in myeloid malignancies, occurring in 10-20% of patients with de novo myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with profound negative impact on outcomes and a median overall survival (OS) of 6-12 months.31 Critically, the clonal burden of TP53 , that is the variant allele frequency (VAF) and/or allelic state of TP53 , is intimately tied with the clinical trajectory of these patients and is a robust, independent predictor of survival.74 Given the poor OS and lack of therapeutic options for TP53 mutant MDS/AML patients, a number of novel agents are being investigated in this patient group.8 Of these, APR-246 has evoked considerable excitement based on its robust clinical efficacy in combination with azacitidine in TP53 mutant MDS/AML patients.109 In this issue of Haematologica ,11 Maslah et al

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