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Therapeutic Strategies and Concepts of Cure in CML

  • Tariq I Mughal
  • John M Goldman
Part of the Hematologic Malignancies book series (HEMATOLOGIC)

Abstract

The molecular basis of chronic myeloid leukemia (CML) has been reasonably well defined in the last 20 years. The acquisition in a hematopoietic stem cell of a BCR-ABL fusion gene is generally considered to be the initiating event for the chronic phase of CML. It leads to expansion of a hematopoietic clone that expresses the Bcr-Abl oncoprotein with enhanced tyrosine kinase activity. Oral administration of the tyrosine kinase inhibitor imatinib mesylate (IM) reduces the leukemia cell mass by at least 2 logs and induces complete cytogenetic remissions in most patients with early phase CML. It probably prolongs survival in comparison with previous treatments, but fails to eradicate leukemia stem cells, some of which may be in a “quiescent” or “dormant” phase. IM is now considered to be the best initial therapy for the majority of patients with newly diagnosed CML, though the issues of optimal dose and duration of treatment are not yet resolved. Some patients who respond initially to IM later become resistant as a result of diverse mechanisms, which include the acquisition of mutations in the BCR-ABL kinase domain. Efforts to improve on the use of IM as a single agent include combining it with other agents and the introduction of second-generation tyrosine kinase inhibitors, such as dasatinib and nilotinib. The therapy of patients in the advanced phases of CML remains a significant challenge.

Keywords

Chronic Myeloid Leukemia Chronic Myelogenous Leukemia Imatinib Mesylate Chronic Myeloid Leukemia Patient Cytogenetic Response 
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 Berlin Heidelberg 2007

Authors and Affiliations

  • Tariq I Mughal
    • 1
  • John M Goldman
    • 2
  1. 1.Division of Hematology and Stem Cell TransplantationUniversity of Texas, Southwestern School of MedicineDallasUSA
  2. 2.Hematology Branch, National Heart, Lung and Blood InstituteNational Institutes of HealthBethesdaUSA

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