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Acute myeloid leukemia

p53 pathway dysfunction is highly prevalent in acute myeloid leukemia independent of TP53 mutational status

Leukemia volume 31, pages 1296–1305 (2017)Cite this article

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Abstract

TP53 mutations are associated with the lowest survival rates in acute myeloid leukemia (AML). In addition to mutations, loss of p53 function can arise via aberrant expression of proteins that regulate p53 stability and function. We examined a large AML cohort using proteomics, mutational profiling and network analyses, and showed that (1) p53 stabilization is universal in mutant TP53 samples, it is frequent in samples with wild-type TP53, and in both cases portends an equally dismal prognosis; (2) the p53 negative regulator Mdm2 is frequently overexpressed in samples retaining wild-type TP53 alleles, coupled with absence of p21 expression and dismal prognosis similar to that of cases with p53 stabilization; (3) AML samples display unique patterns of p53 pathway protein expression, which segregate prognostic groups with distinct cure rates; (4) such patterns of protein activation unveil potential AML vulnerabilities that can be therapeutically exploited.

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    A Quintás-Cardama, Y H Qiu, X Zhang, S M Post & S M Kornblau

  2. Department of Bioengineering, Rice University, Houston, TX, USA

    C Hu & A Qutub

  3. Life Technologies Corporation, Carlsbad, CA, USA

    N Zhang

  4. Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA

    K Coombes

Authors
  1. A Quintás-Cardama
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  2. C Hu
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  3. A Qutub
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  4. Y H Qiu
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  5. X Zhang
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  6. S M Post
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  7. N Zhang
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Correspondence to A Quintás-Cardama or S M Kornblau.

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Quintás-Cardama, A., Hu, C., Qutub, A. et al. p53 pathway dysfunction is highly prevalent in acute myeloid leukemia independent of TP53 mutational status. Leukemia 31, 1296–1305 (2017). https://doi.org/10.1038/leu.2016.350

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