Molecular diagnosis and monitoring in the clinical management of patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors

Am J Hematol. 2008 Apr;83(4):296-302. doi: 10.1002/ajh.21096.

Abstract

The well-established molecular pathogenesis of chronic myelogenous leukemia (CML) and its consequences for laboratory testing and clinical management illustrate a classic paradigm for the importance of molecular diagnostics in targeted drug therapy. The success of the tyrosine kinase inhibitor (TKI), imatinib, as the currently recommended first-line treatment of early chronic phase CML has both fueled the need for timely and reproducible molecular testing of the BCR-ABL1 fusion transcript in diagnosis and monitoring as well as necessitated the detection of kinase domain mutations that confer resistance to this agent. As, ongoing research continues to refine guidelines for monitoring residual disease in patients undergoing TKI therapy, an understanding of molecular technologies and their interpretation is critical. This review summarizes the molecular strategies that are currently employed in the initial diagnosis and subsequent management of CML patients maintained on TKI therapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / blood*
  • Disease Progression
  • Drug Monitoring / methods*
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / blood*
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl