الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Imatinib introduction into CML treatment has transformed a previously fatal disease for many into a manageable chronic illness with excellent long-term survival. Unfortunately, nearly one-third of CML patients have an inferior response to Imatinib, either failing to respond to primary therapy or demonstrating progression after an initial response.
Significant efforts are gathered toward understanding the molecular mechanisms of Imatinib resistance. Among these different mechanisms, the development of resistance inducing mutations is the most relevant. T315I and M351T mutations, among others, are observed more frequently, with T315I mutation being considered the most resistant genotype associated with the highest impact on clinical outcome. In addition, epigenetic mechanisms as abnormal epigenetic regulation of the expression of CML-associated genes may play a critical role in its pathogenesis and in the mechanisms modulating therapeutic responsiveness. DAPK1 is one of the candidate tumor suppressor genes that have been found to be associated with disease progression in patients treated with Imatinib.
The aim of the present work was directed to evaluate the possible effect of DAPK1 gene methylation on treatment response in CML patients and to evaluate the possibility of increased risk of Imatinib resistance in CML patients in case of coexistence of BCR-ABL gene mutations and DAPK1 gene methylation.
In order to achieve these goals, 50 adult CML patients (24 responsive and 26 resistant) were included in the study. A follow-up of 18 months was done to monitor the occurrence of secondary resistance (short lasting response).