格列卫对慢性粒细胞白血病病人Foxo3a和bcr-abl融合基因表达影响

THE INFLUENCE OF GLIVEC ON Foxo3a AND bcr-abl mRNA EXPRESSIONS IN PATIENTS WITH CHRONIC MYELOCYTIC LEUKEMIA

目的探讨初发及格列卫治疗的慢性粒细胞白血病(CML)病人骨髓中转录因子Foxo3a和bcr-abl融合基因的表达及其临床意义。方法采用SYBR GreenⅠ建立的实时荧光RT-PCR的方法,检测18例初发及10例格列卫治疗的CML病人骨髓样本中Foxo3a和bcr-abl融合基因的表达,以GAPDH为内参基因,以行骨髓穿刺排除诊断的非血液病病人的骨髓为对照组;各实验组基因表达水平的差异采用ΔΔCT相对定量法计算。结果初发CML病人骨髓bcr-abl融合基因的表达水平与格列卫治疗组比较差异有显著性(χ2=4.25,P<0.05);3组骨髓样本中Foxo3a的表达水平比较差异均有显著性(χ2=5.73～13.73,P<0.01);且初发CML病人的bcr-abl融合基因的高表达与转录因子Foxo3a的低表达呈明显负相关(r=-0.674,P<0.01)。结论格列卫降低CML病人bcr-abl融合基因表达的同时可以增加Foxo3a的表达;转录因子Foxo3a的低表达与bcr-abl融合基因的高表达密切相关,二者可能共同参与CML的发生。

Objective To investigate the expressions and their clinical significance of transcription factors Foxo3a and bcr-abl fusion gene in patients with initial chronic myelocytic leukemia（CML） and treated with Glivec. Methods Using real-time RT-PCR method created by SYBR GreenⅠ,18 initial CML patients and 10 CML patients treated with Glivec were detected for the expressions of fusion gene of Foxo3a and bcr-abl;taking GAPDH as internal reference gene,those were excluded from the diagnosis of hematopathy,through bone marrow aspiration,were served as controls.The difference of gene expressions among the groups was analyzed by ΔΔCT relative quantity means. Results The difference of expression of bcr-abl mRNA was significant in initial CML patients versus those in Glivec-treated group（χ2=4.25,P0.05）.The difference of expressions of Foxo3a mRNA in bone marrow samples of the three groups was significant（χ2=5.73-13.73,P0.01）;In initial CML,over expression of bcr-abl fusion gene was negatively correlated with low expression of Foxo3a（r=-0.674,P0.01）. Conclusion Glivec decreases the expression of bcr-abl mRNA in CML,and,simultaneously,increases the expression of Foxo3a;the low expression of Foxo3a is closely associated with the over expression of bcr-abl,both of them are likely to be involved in the genesis of this condition.