Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Leuk Res. 2010 Oct;34(10):1255-68. doi: 10.1016/j.leukres.2010.04.016.

BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review.

Author information

  • 1Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.

Abstract

Chronic Myeloid Leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia (Ph+) chromosome and its oncogenic product, BCR-ABL, a constitutively active tyrosine kinase, that is present in >90% of the patients. Epidemiologic data indicates that almost 5000 new cases are reported every year and 10% of these patients eventually succumb to the disease. The treatment of CML was revolutionized by the introduction of imatinib mesylate (IM, Gleevec), a BCR-ABL tyrosine kinase inhibitor (TKI). The clinical use of specific BCR-ABL inhibitors has resulted in a significantly improved prognosis, response rate, overall survival, and patient outcome in CML patients compared to previous therapeutic regimens. However, the complete eradication of CML in patients receiving imatinib was limited by the emergence of resistance mostly due to mutations in the ABL kinase domain and to a lesser extent by molecular residual disease after treatment. The second-generation BCR-ABL TKIs nilotinib (Tasigna) and dasatinib (Sprycel), showed significant activity in clinical trials in patients intolerant or resistant to imatinib therapy, except in those patients with the T315I BCR-ABL mutation. Identifying key components involved in the CML pathogenesis may lead to the exploration of new approaches that might eventually overcome resistance mediated to the BCR-ABL TKIs. Here, we present an overview about the current treatment of Ph+ CML patients with the TKIs and the obstacles to successful treatment with these drugs.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID:
20537386
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk