台灣中部慢性骨髓性白血病病人對於基立克藥物抗藥性之研究

第一種臨床上用於治療慢性骨髓性白血病的BCR-ABL激酶抑制劑已經使用了快5年，基立克(Imatinib mesylate，Greevec)現在是所有新診斷慢性骨髓性白血病病人首選的治療藥劑，但它神奇的效果已經被發展出的臨床抗藥性所遮蓋了，我們嘗試去找出基立克在台灣產生抗藥性的機制。為了評估慢性骨髓性白血病病人對基立克的抗藥性，我們以即時反轉錄多聚合酶鏈反應(Real-time PCR)檢查BCR-ABL致癌基因，並作BCR-ABL激酶區的定序，測定是否出現BCR-ABL基因的突變和放大。所有病人於診斷早期均為BCR-ABL基因陽性，所有病人以基立克(Imatinib mesylate，Greevec)初次治療均達到血液學緩解，只有一個病人經過３年基立克治療達到分子緩解的狀態，另外有２名病人於一年監控期間，產生基立克的抗藥性並復發。兩名復發的病人，其中之一屬於BCR-ABL依賴性抗藥性，另一個屬於BCR-ABL非賴性抗藥性。

The first BCR-ABL kinase inhibitor has been applied to clinical use for chronic myelogenous leukemia (CML) is about five years, Imatinib mesylate is now the first choice treatment for all newly diagnosed CML patient, but the magic efficacy of this drug has been overshadowed by development of clinical resistance. In this study, we try to find out the resistance mechanism of Imatinib in Taiwan. It is due to BCR-ABL kinase domain mutation or BCR-ABL gene over expression or other reason. To access the presence Imatinib resistance in CML, we examined prepheral blood BCR-ABL oncogene of 10 patients with CML by using real-time RT PCR and followed by BCR-ABL kinase domain sequencing, for detecting the presence of BCR-ABL gene mutation or gene over expression. All patients had positive BCR-ABL gene in early diagnose. All patients achieved hematology remission after first-induction chemotherapy with Imatinib mesylate. Only one patient achieved molecular remission after 3 years treatment Imatinib sylatet whereas 2 patients were Imatinib resistance and relapse after1 year monitoring. Of the two relapse patients, one was belong to BCR-ABL dependent resistance and the other was BCR-ABL independent imatinib resistance.