Pushing the limits of targeted therapy in chronic myeloid leukaemia

Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317.


Tyrosine kinase inhibitor (TKI) therapy targeting the BCR-ABL1 kinase is effective against chronic myeloid leukaemia (CML), but is not curative for most patients. Minimal residual disease (MRD) is thought to reside in TKI-insensitive leukaemia stem cells (LSCs) that are not fully addicted to BCR-ABL1. Recent conceptual advances in both CML biology and therapeutic intervention have increased the potential for the elimination of CML cells, including LSCs, through simultaneous inhibition of BCR-ABL1 and other newly identified, crucial targets.

Trial registration: ClinicalTrials.gov NCT00574873 NCT00827138 NCT01207440.

Publication types

  • Review

MeSH terms

  • Animals
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Molecular Targeted Therapy / methods
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism


  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl

Associated data

  • ClinicalTrials.gov/NCT00574873
  • ClinicalTrials.gov/NCT00827138
  • ClinicalTrials.gov/NCT01207440