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BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review.
Leuk Res 2010; 34(10):1255-68LR

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20537386

Citation

An, Xin, et al. "BCR-ABL Tyrosine Kinase Inhibitors in the Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia: a Review." Leukemia Research, vol. 34, no. 10, 2010, pp. 1255-68.
An X, Tiwari AK, Sun Y, et al. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk Res. 2010;34(10):1255-68.
An, X., Tiwari, A. K., Sun, Y., Ding, P. R., Ashby, C. R., & Chen, Z. S. (2010). BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leukemia Research, 34(10), pp. 1255-68. doi:10.1016/j.leukres.2010.04.016.
An X, et al. BCR-ABL Tyrosine Kinase Inhibitors in the Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia: a Review. Leuk Res. 2010;34(10):1255-68. PubMed PMID: 20537386.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. AU - An,Xin, AU - Tiwari,Amit K, AU - Sun,Yibo, AU - Ding,Pei-Rong, AU - Ashby,Charles R,Jr AU - Chen,Zhe-Sheng, PY - 2010/01/21/received PY - 2010/04/25/revised PY - 2010/04/25/accepted PY - 2010/6/12/entrez PY - 2010/6/12/pubmed PY - 2010/10/1/medline SP - 1255 EP - 68 JF - Leukemia research JO - Leuk. Res. VL - 34 IS - 10 N2 - 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. SN - 1873-5835 UR - https://www.unboundmedicine.com/medline/citation/20537386/BCR_ABL_tyrosine_kinase_inhibitors_in_the_treatment_of_Philadelphia_chromosome_positive_chronic_myeloid_leukemia:_a_review_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145-2126(10)00236-5 DB - PRIME DP - Unbound Medicine ER -