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首页> 外文期刊>Gene Therapy and Molecular Biology >Survival assessment and Optimization of BCR/ABL-KD amplification protocol for detection of Imatinib resistant mutations in Ph+ Chronic Myeloid Leukemia patients from Pakistan
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Survival assessment and Optimization of BCR/ABL-KD amplification protocol for detection of Imatinib resistant mutations in Ph+ Chronic Myeloid Leukemia patients from Pakistan

机译：巴基斯坦Ph +慢性粒细胞白血病患者的伊马替尼耐药突变检测的BCR / ABL-KD扩增方案的生存评估和优化

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摘要

Translocation between parts of BCR and ABL genes is the baseline abnormality for chronicmyeloid leukemia (CML) genesis. To overcome this malignancy, Imatinib mesylate, a tyrosine kinase inhibitor (TKI) is being used as the first line treatment option. Certain point mutations arising in the kinase domain of ABL part constitute resistance against drug therapy. By knowing the underlying mutation, resistance can be addressed either by dose adjustment or choosing second generation TKI?s. The present studies aimed to investigate survival probability of patients in relation to their clinical features and to optimize an efficient as well as reliable protocol for RT-PCR based amplification of BCR-ABL kinase domain, and its direct sequencing analysis for mutation detection. Since this procedure has been established for the first time in Pakistan, reproducible and amplifiable products of 1306bp (b2a2) and 1380bp (b3a2), carrying BCR-ABL KD were successfully achieved after trial and error. Their sequencing analysis revealed a total of fourteen point mutations, six in Imatinib responders and eight in resistant CML patients. Thus the mutation detection supported the usefulness of this protocol in both, Imatinib sensitive and resistant patients of chronic myeloid leukemia.
机译：BCR和ABL基因部分之间的易位是慢性粒细胞白血病（CML）发生的基线异常。为了克服这种恶性肿瘤，甲磺酸伊马替尼（一种酪氨酸激酶抑制剂（TKI））被用作一线治疗选择。在ABL部分的激酶结构域中出现的某些点突变构成了对药物治疗的抗性。通过了解潜在的突变，可以通过调整剂量或选择第二代TKI来解决耐药性。本研究旨在调查患者的生存可能性与他们的临床特征有关，并优化基于BCR-ABL激酶域的RT-PCR扩增的有效且可靠的方案，以及用于突变检测的直接测序分析。由于该程序是在巴基斯坦首次建立的，经过反复试验，成功携带BCR-ABL KD的可复制和扩增的产物分别为1306bp（b2a2）和1380bp（b3a2）。他们的测序分析显示总共有14个点突变，伊马替尼应答者中有6个突变，耐药CML患者中有8个。因此，突变检测支持该方案对慢性粒细胞白血病的伊马替尼敏感和耐药患者均有用。

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