BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Protein Kinase Inhibitors

abstract

  • Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones.

publication date

  • May 19, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3597744

Digital Object Identifier (DOI)

  • 10.1038/nature09883

PubMed ID

  • 21593872

Additional Document Info

start page

  • 384

end page

  • 8

volume

  • 473

number

  • 7347