Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant chronic myelogenous leukemia patients

Leuk Res. 2011 Jan;35(1):38-43. doi: 10.1016/j.leukres.2010.06.030. Epub 2010 Jul 29.

Abstract

This report aims to more accurately define the frequency of the involvement of SRC Family Kinases (SFKs) in imatinib- and dasatinib-resistant CML patients. Clinical samples were analysed during in vivo treatment. We confirmed the high frequency of SFKs involvement in Tyrosine kinase inhibitor-resistant CML (52% of the cases) and even further in progressive disease and blast crises (60% of the cases). The SFKs deregulation is also observed in patients harboring BCR-ABL mutations. In T315I and F317L mutated patients, CML-resistance appears to be promoted by SFKs kinase protein reactivation once the BCR-ABL mutated clone has decreased on Omacetaxine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Base Sequence
  • Benzamides
  • Cell Line, Tumor
  • DNA Primers
  • Dasatinib
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl / genetics
  • 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
  • Longitudinal Studies
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*
  • src-Family Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Benzamides
  • DNA Primers
  • Piperazines
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • src-Family Kinases
  • Dasatinib