Unleashing the Guardian: The Targetable BCR-ABL/HAUSP/PML/PTEN Network in Chronic Myeloid Leukemia

Curr Drug Targets. 2017;18(4):389-395. doi: 10.2174/1389450117666160608120527.

Abstract

The complete eradication of Chronic Myeloid Leukemia is still challenging even in the era of highly selective and potent BCR-ABL tyrosine kinase inhibitors (TKIs). The 'Achilles heel' of TKI-based CML therapy is the inability of TKI to effectively target CML stem cells. Several pathways have been described to induce TKI insensitiveness in quiescent CML stem cells. In this review, we will describe the BCR-ABL/HAUSP/PML/PTEN network, whose signaling mediators converge to regulate the function of the tumor suppressor PTEN. We will also highlight the pharmacological strategies to modulate PTEN functions in order to sustain CML stem cell eradication.

Keywords: BCR-ABL; HAUSP; PML; PTEN; chronic myeloid leukemia..

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Neoplastic Stem Cells / drug effects
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Promyelocytic Leukemia Protein / genetics
  • Signal Transduction / drug effects
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin-Specific Peptidase 7

Substances

  • Antineoplastic Agents
  • Promyelocytic Leukemia Protein
  • PML protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7