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Frequency of BCR‑ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib. A final report of the MAPTEST study

doi: 10.20452/pamw.843
pmid: 20010464
Frequency of BCR‑ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib. A final report of the MAPTEST study
The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment.The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM).Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM.Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM.The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.
- Jagiellonian University Poland
- Instytut Hematologii i Transfuzjologi Poland
- Gdańsk Medical University Poland
- Poznan University of Medical Sciences Poland
Adult, Male, mutacje genu BCR‑ABL, DNA Mutational Analysis, Fusion Proteins, bcr-abl, Antineoplastic Agents, Piperazines, chronic myeloid leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Protein Kinase Inhibitors, Chromatography, High Pressure Liquid, Aged, Neoplasm Staging, Dose-Response Relationship, Drug, Gene Expression Regulation, Leukemic, Middle Aged, przewlekła białaczka szpikowa, BCR‑ABL gene mutations, imatinib, Drug Resistance, Neoplasm, Benzamides, Imatinib Mesylate, Female, Poland, imatynib
Adult, Male, mutacje genu BCR‑ABL, DNA Mutational Analysis, Fusion Proteins, bcr-abl, Antineoplastic Agents, Piperazines, chronic myeloid leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Protein Kinase Inhibitors, Chromatography, High Pressure Liquid, Aged, Neoplasm Staging, Dose-Response Relationship, Drug, Gene Expression Regulation, Leukemic, Middle Aged, przewlekła białaczka szpikowa, BCR‑ABL gene mutations, imatinib, Drug Resistance, Neoplasm, Benzamides, Imatinib Mesylate, Female, Poland, imatynib
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