MULTIPLE PATHS TO DRUG RESISTANCE PHENOTYPE IN CHRONIC MYELOID LEUKEMIA PATIENTS UNDERGOING IMATINIB MESYLATE TREATMENT

The introduction of Imatinib mesylate (Gleevec/Glivec) to the therapeutic armamentarium has changed the current management of Chronic Myeloid Leukemia (CML) patients. Despite being the first line treatment for CML, resistance to Imatinib is emerging as a real clinical problem in the management of CM...

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Bibliographic Details
Published in:Anticancer research 2008-10, Vol.28 (5C)
Main Authors: Ankathil, R, Zanry, M K, Hassan, R, Dzarr, A, Peng, H B, Baba, A A
Format: Article
Language:English
Online Access:Get full text
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Summary:The introduction of Imatinib mesylate (Gleevec/Glivec) to the therapeutic armamentarium has changed the current management of Chronic Myeloid Leukemia (CML) patients. Despite being the first line treatment for CML, resistance to Imatinib is emerging as a real clinical problem in the management of CML. Therapeutic resistance to Imatinib may be primary or secondary. Resistance development is a multifactorial phenomenon in patients with CML, mediated by a diversity of mechanisms. There are two broad mechanisms of resistance (1) BCR-ABL dependent and (2) BCR-ABL independent. BCR-ABL dependent pathways include ABL kinase domain mutations and BCR-ABL amplification. Data on cytogenetic and molecular response of 42 CML patients treated with Imatinib, at Hospital University Sains Malaysia and the data on dHPLC based mutation analysis performed on 16 CML patients showing signs of disease resistance will be presented. BCR-ABL independent pathways may include several mechanisms. Various genetic and epigenetic alterations are proposed as candidate mechanisms involved in BCR-ABL independent pathways to IM resistance in CML patients and these multiple paths to IM resistance phenotype will also be discussed.
ISSN:0250-7005