The importance of T315I, F317L, E255K, And Y253H Bcr-Abl gene mutations in the patients of chronic myeloid leukemia who treated by imatinib

Chronic Myeloid Leukemia (CML); is a Malign Hemotopoetic stem cell disease which concluded by the fusions of BCR and ABL genes. It is characterized by the existence of the Philedelphia translocations t (9;22) (q34;q11). In spite of Imatinib is an effective treatment for CML, the important problem that is seen by at the patients is primary and secondary resistance.In this study, the 54 chronic phase CML patients observed in two centre between 2000-2008, mostly observed (in the place of imatinib connection) T315I, F317L, Y253H mutations in ABL gene and E255K mutation observed in the gene?s connection place of P-loop phosphate are scanned by the method of allel specific oligonükleotit-polimeraz chain reaction (ASO-PCR) and proved by the SSCP method.12 of patients are men and 42 of patients are women and the median age of the patients are 44.5 (19-78). According to the Sokol classification in diagnosis; 12 of patients (22.2%) are low risky, 26 of them (48.1%) are middle risky and 16 of them (29.6%) are in high risky group. Median imatinib usage time is 1.8 (0.3-7) year. When imatinib treatment response is evaluated; the 24 (%44.4) of the patients are optimal response, 10 (18.5%) of the patients are suboptimal response and 20 (37%) of them have resistance.Median overall survival (OS) and progression free survival (PFS) can not be obtained yet. Expected values in 7 years are found as 96% for OS and 80% for PFS. Scanned mutations are observed in 18 (33.3%) of the patients. Despite T315I is observed in 11 (20.3%) and F317L is in 9 (16.6%) patients, Y253H and E255K mutations did not observe. In 2 (3.7%) of the mutation determined patients, T315I and F317L mutations are observed together. Mutations are determined in 60% of the resistance patients (p=0.004). 7 years PFS is found as 62% in mutation determined patients and 90% in mutation undetermined patients (p=0.041). While T3151 mutation observed patients guided to AKIT, F317L mutation observed patients are started to nilotinib and dasatinib treatment.To determine the optimal treatment type; resistance should be identified in early stages in CML patients, rational treatment type should be planned according to the determined mutation type.Keywords: Chronic Myeloid Leukemia, BCR-ABL Nokta Mutasyonu, ImatinibThis study is supported by the Gaziantep University Research Fund (TF 08.01).