Talk:Philadelphia chromosome

2008

Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia

Leuk Lymphoma. 2008 Jan;49(1):19-26.

Li S.

The Jackson Laboratory, Bar Harbor, ME 04609, USA. shaoguang.li@jax.org Abstract The BCR-ABL kinase inhibitor imatinib has shown significant efficacy in chronic myeloid leukemia (CML) and is the standard front-line therapy for patients in chronic phase. However, a substantial number of patients are either primarily refractory or acquire resistance to imatinib. While a number of mechanisms are known to confer resistance to imatinib, increasing evidence has demonstrated a role for BCR-ABL-independent pathways. The Src-family kinases (SFKs) are one such pathway and have been implicated in imatinib resistance. Additionally, these kinases are key to the progression of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The dual SFK/BCR-ABL inhibitor dasatinib is now clinically available and has markedly greater potency compared with imatinib against native BCR-ABL and the majority of imatinib-resistant BCR-ABL mutants. Therefore, this agent, as well as other dual SFK/BCR-ABL inhibitors under development, could provide added therapeutic advantages by overcoming both BCR-ABL-dependent (i.e. BCR-ABL mutations) and -independent forms of imatinib resistance and delaying transition to advanced phase disease. In this review, we discuss the preclinical and clinical evidence demonstrating the involvement of SFKs in imatinib resistance and the progression of CML and Ph+ ALL, as well as the potential role of dual SFK/BCR-ABL inhibition in the management of these diseases.

PMID: 18203007 http://www.ncbi.nlm.nih.gov/pubmed/18203007

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430171

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Historic Papers

THE DISTRIBUTION OF THE PHILADELPHIA CHROMOSOME IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA

WHANG J, FREI E 3rd, TJIO JH, CARBONE PP, BRECHER G. Blood. 1963 Dec;22:664-73. No abstract available. PMID: 14084628 [PubMed - indexed for MEDLINE]Free Article

Chronic granulocytic leukemia and the Philadelphia chromosome

FITZGERALD PH, ADAMS A, GUNZ FW. Blood. 1963 Feb;21:183-96. No abstract available. PMID: 13945361 [PubMed - indexed for MEDLINE]Free Article

The Philadelphia Chromosome and Leukemia

[No authors listed] Can Med Assoc J. 1961 May 20;84(20):1142. No abstract available. PMID: 20326755