LAUSR

ABSTRACT Introduction: TP53 mutations in acute myeloid leukemia (AML) are associated with poor response to standard chemotherapy and high rates of relapse, even after allogeneic stem cell transplantation. The mutated p53 protein is likely to be significant for leukemogenesis and chemosensitivity in human AML. Areas covered: Relevant publications were identified through literature searches (using terms ‘acute myeloid leukemia’ plus ‘TP53’ or ‘p53’) in the PubMed database. We searched for original articles and reviews describing the biology and effects of antileukemic therapy in this AML variant. Expert opinion: TP53 mutations are associated with adverse prognoses in several malignancies, including AML. A wide range of such mutations has been described in human cancers; we give an overview of these mutations and their reported functional consequences. TP53 mutations can be associated with mutation-induced dependencies (e.g. a signaling pathway) for survival/proliferation or gain of new biological functions/characteristics. Finally, based on the current knowledge we discuss experimental and clinical observations from other malignancies that are most likely to be relevant for AML and the possible consequences of these observations for future treatment of TP53-mutated AML. In the final section, we focus on relevant targeted therapies that are now being considered for use in AML.