ABL-Kinase Mutations in Progenitors and Stem Cells from Chronic Myeloid Leukemia Patients

  • Jean-Claude Chomel
  • Nathalie Sorel
  • Ali G. Turhan
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 8)

Abstract

Tyrosine kinase inhibitors (TKIs) have profoundly changed the natural history and prognosis of chronic myeloid leukemia (CML). However, a small proportion of patients develop a resistance towards targeted therapies. Missense mutations located within the kinase domain of the BCR-ABL oncogene (also referred to as BCR-ABL mutations or ABL-kinase mutations) are the most common mechanism of resistance. Although it has clearly been established that genetic instability inherent to BCR-ABL expressing leukemic cells predisposes the latter to the acquisition of mutations, the hierarchical distribution of these mutations in stem cells was not known until recently. There is now evidence suggesting that ABL-kinase mutations occur in hematopoietic progenitors and stem cells expressing the BCR-ABL oncogene, adding therefore an increased level of complexity to the phenomenon of TKI-resistance in CML stem cells.

Keywords

Chronic Myeloid Leukemia Chronic Myeloid Leukemia Patient Leukemic Stem Cell Chronic Myeloid Leukemia Cell Imatinib Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Jean-Claude Chomel
    • 1
  • Nathalie Sorel
    • 1
  • Ali G. Turhan
    • 1
  1. 1.Service d’Hématologie et Oncologie Biologique, CHU de Poitiers, Inserm U935Université de PoitiersPoitiersFrance

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