抗凋亡基因bcl-X_L与白血病细胞耐药的相关性研究

Relationship of anti-apoptosis gene bcl-X_L and multidrug resistance in leukemia cells

目的：研究ｂｃｌ－ＸＬ基因高表达在白血病细胞耐药形成中的作用，观察急性髓细胞白血病病人的ｂｃｌ－ＸＬ表达与临床疗效间的相关性。方法：采用脂质体法将 ｂｃｌ－ＸＬ ｃＤＮＡ转导入ＨＬ－６０细胞；流式细胞仪定量检测凋亡细胞；ＭＴＴ法测定足叶乙甙、柔红霉素、阿霉素对转染细胞的细胞毒性； ＲＴ－ＰＣＲ法检测２０例急性髓细胞白血病病人的 ｂｃｌ－Ｘ_Ｌ表达。结果：ｂｃｌ－Ｘ_Ｌ高表达可抑制足叶乙甙诱发的凋亡，抑制率为４０．５％；降低上述化疗药物的细胞毒作用，耐药指数分别为３．２、３．２、１．６。１６／２０例急性髓细胞白血病病人ｂｃｌ－ＸＬ阳性，其中７例ｂｃｌ－ＸＬ强阳性表达，仅２例（２８．６％）获得完全缓解；９例ｂｃｌ－Ｘ_Ｌ弱阳性表达，６例（６６．７％）获得完全缓解。结论：ｂｃｌ－Ｘ_Ｌ可能作为一种新的耐药途径，通过抑制化疗药物诱发的细胞凋亡参与多药耐药的形成，可以作为预测耐药及判定预后的一种参考指标。

Objective: To investigate the role of bcl-XL gene in development of multidrug resistance and to observe the relationship between the expression of bcl-X_L in acute myeloid leukemia and clinical response. Methods: bcl-X_L. eDNA was transfected into HL-60 cells using lipofictamine. The apoptotic rate was quantitatively analyzed with FCM. The cytotoxicity of chemotherapy drugs in vitro was compared employing the MTT assay. RT-PCR was applied to detect the expression of bcl-X_L. in 20 patients with acute myeloid leukemia. Results: The overexpression of bcl-XL in HL-60 cells inhibited the etoposide-induced apoptosis by 40. 5% and decreased the cytotoxicity of etoposide. daunorubicin and adriamycin. The resistance factors were 3. 2, 3. 2, 1. 6, respectively. Sixteen of 20 patients with acute myeloid leukemia expressed bcl-X_L mRNA. Only 2/7 (28. 6% )cases with higher level of bcl-X_L mRNA achieved complete remission, while 6/9 (66. 8% ) cases with lower level of bcl-X_L mRNA got complete remission. Conclusion: bcl-X_L gene might he involved a new multidrug resistance phenotype through inhibiting the apoptosis induced by chemotherapeutic agents. The detection of bcl-X_L gene also provides a new parameter to predict The prognosis of acute myeloid leukemia.