IFN-a及其联合GMCSF对CML患者骨髓细胞凋亡相关基因表达的影响  

Influence of IFN-a and IFN-a combined with GM-CSF on expression of the genes related to cell apoptosis of MNCs from bone marrow in CML patients

作　　者：汤立军[1] 陈汉春 彭兴华 罗志勇 罗赛群 陈方平[2] 

机构地区：[1]分子生物学研究中心，长沙 410078 [2]附属湘雅医院血液科，长沙 410008

出　　处：《湖南医科大学学报》2000年第6期570-572,共3页Bulletin of Hunan Medical University

基　　金：国家自然科学基金资助项目(39570805);中华医学基金(99698)

摘　　要：目的 :探讨IFN α及IFN α联合GM CSF调节慢性期慢性粒细胞白血病 (CML CP)患者骨髓单个核细胞(MNCs) bcr abl,bcl 2 和 c myc基因表达的影响。方法 :淋巴细胞分离液离心富集 14例CML CP患者骨髓MNCs,经干扰素 α(IFN α)及IFN α联合粒细胞 -巨噬细胞集落刺激因子 (GM CSF)培养 2 4h后 ,采用相对定量逆转录 -聚合酶链反应 (RT PCR)及扩增片段光密度扫描分析bcr abl,bcl 2 ,c myc及β actin 基因表达水平 ,配对t检验统计分析组间差异。结果 :IFN α(2 0 0U·ml-1)及IFN α(2 0 0U·ml-1)联合GM CSF(10ng·ml-1)均显著抑制bcr abl基因表达 ;IFN α部分抑制 c myc及 bcl 2 基因表达 ;GM CSF在IFN α作用的基础上部分促进 bcr abl及 c myc基因表达和显著抑制 bcl 2 基因表达。结论 :IFN α及IFN α联合GM CSF均可抑制抗凋亡基因bcr abl和bcl 2基因表达 ,并调节c myc基因表达水平。通过促进细胞凋亡而抑制恶性克隆增长是IFN α或IFN α联合GM CSF治疗CML的可能作用机制。Objective: To investigate the effects of interferon α(IFN α) and IFN α combined with granulocytic macrophage colony stimulating factor(GM CSF) on expression of bcr abl, bcl 2 and c myc genes in the mononuclear cells(MNCs) from bone marrow(BM) of the patients with chronic myelogenous leukemia at chronic phase(CML CP). Methods: The MNCs were collected from bone marrow of 14 CML CP patients by centrifugalization in lymphocyte separation medium, and cultivated in the medium with IFN α and IFN α plus GM CSF for 24 hours. The expression levels of bcr abl, bcl 2, c myc and β actin were detected by using relatively quantitative reverse transcriptase polymerase chain reaction (RT PCR) and optical density scanning technology for the amplified fragments. The statistical differences between each inducing experimental group and the control were analyzed by t test in pairs. Results: Both IFN α (200?U·ml -1 ) and IFN α combined with GM CSF (10?ng·ml -1 ) significantly inhibited bcr abl gene expression, meanwhile IFN α partially suppressed c myc and bcl 2 gene expression, and GM CSF significantly inhibited bcl 2 gene expression but partially upregulated bcr abl and c myc gene expression levels on the basis of IFN α effects. Conclusions: Both IFN α and IFN α plus GM CSF can inhibit the expresson of anti apoptosis gene such as bcr abl and bcl 2, and regulate the expression of c myc. It is the possible mechanism of IFN α therapy or combined therapy on CML at chronic phase that the malignant clone expansion is inhibited by promoting apoptotic cell death. [

关 键 词：慢性髓细胞性白血病 IFNa GM-CSF 细胞凋亡 

分 类 号：R730.2[医药卫生—肿瘤]