Significance of the T3151, T317L, E255K AND Y253H BCR-ABL gene mutations in Philadelphia positive Chronic Myeloid Leukemia patients

Year 2016, Volume: 11 Issue: 2, 0 - 0, 08.12.2016

Sacide Pehlivan , Cem Kis Bulent Eser Mehmet Yılmaz Leylagul Kaynar , Sibel Oguzkan Balcı , Mustafa Cetin Mustafa Pehlivan

Abstract

In this study it has been aimed to scan the most frequently observed  types of mutations in imanitib treated Philadelphia positive (Ph+) Chronic Myelositer Leukemia (CML) patients, namely the T315I, F317L, Y253H, and the P-Ioop phosphate binding region E255K mutations,   in order to demonstrate any significant correlation between the  presence  of  these mutations and the estimations on  the relevant clinical parameters. Fifty four chronic phase (CP) CML patients attending two separate centers between 2000 and 2008 were included in this study, after scanning by the ASO-PCR method, to be positive for T315I, F317L, Y253H and E255K mutations in the BCR-ABL gene. Twenty of the patients were men and 42 were women with a median age of 44.5 (19-78). According to the Sokol classification for diagnosis, 12 cases (22.2%) were in the low risk, 26 (48.1%) were in the middle risk and 16 (29.6%) were in the high risk group. Median time of imatinib usage was 1.8 (0.3-7) years. Response to imatinib treatment was optimal in 24 (%44.4) of the patients and suboptimal in 10 (18.5%) of the patients, while 20 (37%) showed resistance. Expected values in 7 years were found to be 96% for median overall survival (OS) and 80% for progression-free survival (PFS). Scanned mutations were observed in 18 (33.3%) patients and T315I and F317L together were detected in 2 patients. Mutations were detected in 60% (p=0.004) of the imatinib resistant patients and the 7-year PFS in this group was 62%, while it was 90% (p=0.041) in patients without detected mutations. While patients with T3151 mutation were recommended allogeneic stem cell transplantation, patients with F317L mutation were started on nilotinib and dasatinib treatment. To determine the optimal treatment type; resistance should be identified in early stages in CML patients and the rational treatment should be planned according to the determined mutation type.

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