BCR-ABL promotes PTEN downregulation in chronic myeloid leukemia

PLoS One. 2014 Oct 24;9(10):e110682. doi: 10.1371/journal.pone.0110682. eCollection 2014.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel not recurrent N212D-PTEN point mutation found in the EM2 blast crisis cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blast Crisis / metabolism
  • Blast Crisis / pathology
  • Cell Line, Tumor
  • Down-Regulation*
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Mice
  • NIH 3T3 Cells
  • PTEN Phosphohydrolase / metabolism*

Substances

  • Fusion Proteins, bcr-abl
  • PTEN Phosphohydrolase
  • PTEN protein, human

Grants and funding

This research was supported by Giovani Ricercatori-Ricerca Finalizzata, ministero della salute 2010 to AM, and AIRC to GS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.