High Δnp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia

Antonio R. Lucena-Araujo, Haesook T. Kim, Carolina Thomé, Rafael H. Jacomo, Raul A. Melo, Rosane Bittencourt, Ricardo Pasquini, Katia Pagnano, Ana Beatriz F Glória, Maria De Lourdes Chauffaille, Melina Athayde, Carlos S. Chiattone, Ingrid Mito, Rodrigo Bendlin, Carmino Souza, Cristina Bortolheiro, Juan L. Coelho-Silva, Stanley L. Schrier, Martin S. Tallman, David GrimwadeArnold Ganser, Nancy Berliner, Raul C. Ribeiro, Francesco Lo-Coco, Bob Löwenberg, Miguel A. Sanz, Eduardo M. Rego

Research output: Contribution to journalArticlepeer-review

Abstract

The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (DNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between DNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ΔNp73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ΔNp73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P 5 .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical responsein APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.

Original languageEnglish
Pages (from-to)2302-2306
Number of pages5
JournalBlood
Volume126
Issue number20
DOIs
Publication statusPublished - Nov 12 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

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