The role of TP53 in acute myeloid leukemia: Challenges and opportunities.

Genes, Chromosomes & Cancer
Karina BarbosaAniruddha J Deshpande

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 increas...Continue Reading

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Jan 11, 2020·Current Opinion in Hematology·Hannah Asghari, Chetasi Talati
Jul 30, 2020·Current Oncology Reports·Maya AbdallahKah Poh Loh
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Apr 27, 2021·HemaSphere·Alexandre FagnanJuerg Schwaller
May 1, 2021·Leukemia & Lymphoma·Jacqueline WallwitzDagmar Stoiber

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