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Functional classification of TP53 mutations in acute myeloid leukemia

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Item Type:Article
Title:Functional classification of TP53 mutations in acute myeloid leukemia
Creators Name:Dutta, S. and Pregartner, G. and Rücker, F.G. and Heitzer, E. and Zebisch, A. and Bullinger, L. and Berghold, A. and Döhner, K. and Sill, H.
Abstract:Mutations of the gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15-4.0; = 0.017) and EFS (HR, 1.97; 95% CI, 1.06-3.69; = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.
Keywords:Acute Myeloid Leukemia, TP53 Mutations, Functional Classification, Relative Fitness Core, Prognosis
Page Range:637
Date:10 March 2020
Official Publication:https://doi.org/10.3390/cancers12030637
PubMed:View item in PubMed

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