Mutation in the ATP-binding Site of BCR-ABL in a Patient With Chronic Myeloid Leukaemia With Increasing Resistance to STI571

Br J Haematol. 2002 Oct;119(1):109-11. doi: 10.1046/j.1365-2141.2002.03708.x.

Abstract

The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr-Abl kinase domain. This was a G to A transition that resulted in a glutamic acid to lysine substitution at position 255 (E255K) in the Abl type 1a protein. We suggest that the acquisition of point-mutations in the tyrosine kinase domain of Bcr-Abl may cause progressive clinical resistance to STI571.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Amino Acid Substitution / genetics
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Drug Resistance, Neoplasm / genetics
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Piperazines / therapeutic use*
  • Point Mutation / genetics*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / therapeutic use*

Substances

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