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Monitoring BCR-ABL Fusion Gene by Real Time Quantitative PCR in Chronic Myelogenous Leukemia Patients Treated with Imatinib Mesylate

Author: XiaoJian
Tutor: LiuZuo
School: Sichuan University
Course: Internal Medicine
Keywords: Real Time Quantitative PCR chronic myelogenous leukemia imatinib mesylate BCR-ABL fusion gene resistance mechanism
CLC: R733.7
Type: Master's thesis
Year: 2007
Downloads: 107
Quote: 0
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Abstract


Objective To monitor BCR-ABL fusion gene of chronic phase chronic myelogenous leukemia(CML-CP) dynamically, so as to evaluate the CML-CP patients’ response to imatinib mesylate. Some initial approaches will be done to find the resistance mechanism for patients who developed secondary resistance during treated with imatinib as frontline therapy.Material and Methods BCR-ABL fusion gene mRNA levels were continuously monitored by Real Time Quantitative PCR (RQ-PCR) technique, and 110 samples from 30 CML patients were collected on the time points of pre-treated and every 3 months post-treated with imatinib. The results of RQ-PCR were compared with those of cytogenetics, bone marrow and clinical situations in order to get some message of correlation among these factors. For patients who developed secondary resistance, MDR1 gene mRNA levels were also monitored by RQ-PCR technique and point mutation were detected by a reverse transcription-polymerase chain reaction (RT-PCR) strategy to amplify and sequence the ABL kinase domain of BCR-ABL.Results Most patients’ BCR-ABL levels decreased significantly after treated with imatinib, while 5 patients were not. One of these five patients’ BCR-ABL levels decreased when increased the dose of imatinib to 600 mg/d. Two of these five patients (patient 7 and patient 12) could be defined as secondary resistance according to clinical manifestations, drug usages and other associated examinations. Exact point mutations couldn’t be found in these two patients. But their MDR1 level increased gradually during the therapy. For patient 7 this level increased dramatically after drug dose increased, so the exact mechanism for its resistance still remained for further research. For patient 12 who’s MDR1 level increased earlier than the level of BCR-ABL, could we think its resistance was related with MDR1 gene’s over expression?Conclusion This study suggested that:1, Monitor the BCR-ABL fusion gene levels for CML-CP patients treated with imatinib by RQ-PCR is reliable and wll be helpful for therapy methods chosen.2, Imtinib can effectively suppress leukemic cell proliferation. CML-CP patients who respond well to imatinib will rarely develope secondary resistance. Some patients develope accelerate period could get relief again when imatinib dosage increased.3, Kinase domain mutations in BCR-ABL represent the most common mechanism of secondary resistance to imatinib. Different mutation area show different responses to imatinib and different therapy strategies should be considered. Other mechanisms of imatinib resistance couldn’t be neglected. Systematic examinations are expected to establish for imatinib resistance.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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