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Review
. 2019 Dec;58(12):875-888.
doi: 10.1002/gcc.22796. Epub 2019 Sep 3.

The Role of TP53 in Acute Myeloid Leukemia: Challenges and Opportunities

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Review

The Role of TP53 in Acute Myeloid Leukemia: Challenges and Opportunities

Karina Barbosa et al. Genes Chromosomes Cancer. .

Abstract

The tumor suppressor gene TP53 is one of the most frequently mutated genes in human cancer. The central role of the TP53 protein in several fundamental processes such as cancer, aging, senescence, and DNA repair has ensured enormous attention. However, the role of TP53 in acute myeloid leukemia (AML) is enigmatic. Unlike many other human cancers, a vast majority of AMLs display no genomic TP53 alterations. There is now growing appreciation of the fact that the unaltered TP53 status of tumor cells can be exploited therapeutically. As most AMLs have an intact TP53 gene, its physiological tumor-suppressive roles could be harnessed. Therefore, the use of pharmacological activators of the TP53 pathway may provide clinical benefit in AML. Conversely, even though the frequency of TP53 mutations in AML is substantially lower than in other human cancers, TP53 mutations are associated with chemoresistance and high risk of relapse. In patients with TP53 mutations, these alterations may lead to novel, selective vulnerabilities, creating opportunities for therapeutic targeting of TP53 mutant AML. The mutational status of TP53 therefore poses challenges and opportunities in terms of advancing effective treatment strategies in AML. An increasing armamentarium of small-molecule activators of the TP53 pathway, and a growing understanding of molecular pathways triggered by mutant TP53 have accelerated efforts aimed at targeting TP53 function in AML. In combination with standard AML chemotherapy or emerging targeted therapies, pharmacological targeting of the TP53 pathway may provide therapeutic benefit in AML.

Keywords: P53; TP53; acute myeloid leukemia; leukemia; therapy.

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