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TP53 Gene Mutations and Azacitidine Response in AML

By: Anna Nowogrodzki
Posted: Monday, December 7, 2020

TP53 mutation was found to be associated with worse survival but not with a response to azacitidine in patients with acute myeloid leukemia (AML), according to a recent study. Eric Delabesse, MD, of the Centre Hospitalier Universitaire de Toulouse, France, and colleagues published their results in PLOS One.

“Regarding the growing field of TP53-activating compounds and targeted therapy against TP53 pathway genes (eg, MDM2), a better characterization of mutational and nonmutational TP53 alterations will become useful in the initial workup of each acute myeloid leukemia patient,” the authors wrote.

The study included 279 patients treated with azacitidine between 2007 and 2016 who were prospectively enrolled in Toulouse's regional healthcare network. The patients’ median age was 76. The authors performed genetic screening on 224 of the patients. Of them, 55 (24.6%) had TP53 mutations, and almost all of them (53) had high-risk cytogenetics. A total of 109 patients had an adverse karyotype.

The authors found that TP53 mutations were associated with worse survival, but they had no apparent association with azacitidine response. This was true even for patients with an adverse karyotype. The authors selected three different recently validated classification systems that categorized TP53 mutations by their functional roles in tumor suppression, but none of these three systems could identify subgroups of patients who were more likely to benefit from azacitidine.

Future studies might investigate whether or not TP53 mutations are associated with decitabine treatment outcomes, the authors noted. Research could also examine whether a TP53-mutant classification may be linked to outcomes from induction chemotherapy.

Disclosure: The study authors’ disclosure information may be found at journals.plos.org.


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