Mat Yusoff Yuslina, Abu Seman Zahidah, Othman Norodiyah, Kamaluddin Nor Rizan, Esa Ezalia, Zulkiply Nor Amalina, Abdullah Julia, Zakaria Zubaidah
Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Wilayah Persekutuan Kuala Lumpur, Malaysia. Email:
Asian Pac J Cancer Prev. 2018 Dec 25;19(12):3317-3320. doi: 10.31557/APJCP.2018.19.12.3317.
Objective: Chronic Myeloid Leukemia (CML) is caused by a reciprocal translocation between chromosomes 9 and 22, t(9;22) (q34;q11) which encodes for the BCR-ABL fusion protein. Discovery of Imatinib Mesylate (IM) as first line therapy has brought tremendous improvement in the management of CML. However, emergence of point mutations within the BCR-ABL gene particularly T315I mutation, affects a common BCR-ABL kinase contact residue which impairs drug binding thus contribute to treatment resistance. This study aims to investigate the BCR-ABL T315I mutation in Malaysian patients with CML. Methods: A total of 285 patients diagnosed with CML were included in this study. Mutation detection was performed using qualitative real-time PCR (qPCR). Results: Fifteen out of 285 samples (5.26%) were positive for T315I mutations after amplification with real-time PCR assay. From the total number of positive samples, six patients were in accelerated phase (AP), four in chronic phase (CP) and five in blast crisis (BC). Conclusion: Mutation testing is recommended for choosing various tyrosine kinase inhibitors (TKIs) to optimize outcomes for both cases of treatment failure or suboptimal response to imatinib. Therefore, detection of T315I mutation in CML patients are clinically useful in the selection of appropriate treatment strategies to prevent disease progression.
慢性髓性白血病（CML）由9号和22号染色体之间的相互易位t(9;22)(q34;q11)引起，该易位编码BCR-ABL融合蛋白。甲磺酸伊马替尼（IM）作为一线治疗药物的发现给CML的治疗带来了巨大改善。然而，BCR-ABL基因内点突变的出现，特别是T315I突变，影响了常见的BCR-ABL激酶接触残基，损害了药物结合，从而导致治疗耐药。本研究旨在调查马来西亚CML患者中的BCR-ABL T315I突变。方法：本研究共纳入285例确诊为CML的患者。使用定性实时PCR（qPCR）进行突变检测。结果：在285个样本中，有15个（5.26%）在实时PCR检测扩增后T315I突变呈阳性。在阳性样本总数中，6例患者处于加速期（AP），4例处于慢性期（CP），5例处于急变期（BC）。结论：建议进行突变检测，以选择各种酪氨酸激酶抑制剂（TKIs），从而优化治疗失败或对伊马替尼反应欠佳的病例的治疗结果。因此，检测CML患者中的T315I突变在选择合适的治疗策略以预防疾病进展方面具有临床实用性。
