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[慢性髓性白血病错配修复基因的研究]

[Study on mismatch repair genes of chronic myeloid leukemia].

作者信息

Luo Jun, Peng Zhi-gang, Chen Yan, Lai Yong-rong, Lu Yu-ying, Song Shan-jun

机构信息

Department of Hematology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2006 Feb;27(2):103-6.

Abstract

OBJECTIVE

To investigate the expression and regulation mechanism of mismatch repair (MMR) genes in chronic myeloid leukemia (CML).

METHODS

Expression of MMR genes hMSH2, hMSH3, hMSH6, hMLH1 and hPMS2 mRNAs in 62 CML patients and K562 cell line were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of bcr-abl mRNA and MMR genes mRNA were detected by RT-PCR in 26 CML patients with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) and 4 CML patients on imatinib treatment. Expression of bcr-abl mRNA was detected by RT-PCR and tyrosine phosphorylation of BCR-ABL fusion protein by Western blot.

RESULTS

Expression of hMSH2, hMSH3 and hMLH1 mRNA was significantly lower in CML and K562 cells than in normal control (P < 0.05). In 26 CML with allo-PBSCT and 4 CML patients on imatinib treatment, expressions of hMSH2, hMSH3 and hMLH1 mRNA was enhanced while expression of bcr-abl mRNA decreased. In CML MNC after imatinib treatment and in K562 cells, expression of hMSH2, hMSH3 and hMLH1 mRNA was enhanced while tyrosine phosphorylation of BCR-ABL fusion protein decreased.

CONCLUSION

Expressions of hMSH2, hMSH3 and hMLH1 mRNA were down-regulated by bcr-abl fusion gene.

摘要

目的

探讨错配修复(MMR)基因在慢性髓性白血病(CML)中的表达及调控机制。

方法

采用半定量逆转录聚合酶链反应(RT-PCR)检测62例CML患者及K562细胞系中MMR基因hMSH2、hMSH3、hMSH6、hMLH1和hPMS2 mRNA的表达。采用RT-PCR检测26例接受异基因外周血干细胞移植(allo-PBSCT)的CML患者及4例接受伊马替尼治疗的CML患者中bcr-abl mRNA和MMR基因mRNA的表达。采用RT-PCR检测bcr-abl mRNA的表达,采用蛋白质印迹法检测BCR-ABL融合蛋白的酪氨酸磷酸化。

结果

CML及K562细胞中hMSH2、hMSH3和hMLH1 mRNA的表达明显低于正常对照(P<0.05)。在26例接受allo-PBSCT的CML患者及4例接受伊马替尼治疗的CML患者中,hMSH2、hMSH3和hMLH1 mRNA的表达增强,而bcr-abl mRNA的表达降低。在伊马替尼治疗后的CML单个核细胞及K562细胞中,hMSH2、hMSH3和hMLH1 mRNA的表达增强,而BCR-ABL融合蛋白的酪氨酸磷酸化降低。

结论

bcr-abl融合基因下调hMSH2、hMSH3和hMLH1 mRNA的表达。

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