State-of-the-art in the treatment of chronic myeloid leukaemia

Curr Opin Oncol. 2008 Jan;20(1):112-21. doi: 10.1097/CCO.0b013e3282f1fe8a.

Abstract

Purpose of review: To revise the current goals of therapy of chronic myeloid leukaemia and to incorporate the influence of the underlying chronic myeloid leukaemia biology on directing therapeutic management.

Recent findings: The management of chronic myeloid leukaemia has been revolutionized by targeted molecular therapy that inhibits the ABL kinase activity of the BCR-ABL gene. The achievement of a major molecular response with the first tyrosine kinase inhibitor to be introduced into clinical practice, imatinib, is a focus of therapeutic regimens. Second-generation tyrosine kinase inhibitors are available that have more potent effects than imatinib, and have activity against imatinib-resistant subclones. Strategies to overcome the restoration of BCR-ABL signalling and subsequent resistance to therapy include imatinib dose escalation, a more potent tyrosine kinase inhibitor, as well as non-BCR-ABL-dependent approaches and agents in clinical development.

Summary: Therapeutic advances in chronic myeloid leukaemia continue to circumvent the challenges of drug resistance and the minimal residual leukaemic burden providing effective strategies for future therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Genes, abl
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Mutation
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Stem Cells / metabolism
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • nilotinib