High Δnp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia Academic Article uri icon

Overview

MeSH Major

  • Alternative Splicing
  • DNA-Binding Proteins
  • Gene Expression Regulation, Leukemic
  • Leukemia, Promyelocytic, Acute
  • Models, Biological
  • Nuclear Proteins
  • Tumor Suppressor Proteins

abstract

  • The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (ΔNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between ΔNp73 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 = .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.

publication date

  • November 12, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4760128

Digital Object Identifier (DOI)

  • 10.1182/blood-2015-01-623330

PubMed ID

  • 26429976

Additional Document Info

start page

  • 2302

end page

  • 6

volume

  • 126

number

  • 20