急性白血病患者骨髓细胞CHFR基因表达及其临床意义

Expression of mitosis checkpoint gene CHFR in acute leukemia

目的:探讨成人急性白血病(AL)患者骨髓细胞中有丝分裂早期稽查点CHFR基因的。方法 采用流式细胞术检测HL 60细胞的细胞周期,逆转录聚合酶链反应对65例初治(45例)及复发(20例)的AL患者进行CHFR基因mRNA水平的检测,对其中32例AL患者,用免疫印迹法检测CHFR蛋白表达水平。8名正常人作为对照。结果 (1)CHFR蛋白表达水平与S期细胞所占比例相关。(2) 60 .0% ( 27 /45 )的AL患者CHFR基因mRNA表达水平和40. 6% ( 13 /32)的AL患者CHFR的蛋白表达水平明显低于正常对照相。( 3 )复发组急性淋巴细胞性白血病(ALL)患者的CHFR蛋白中位表达水平(0 .71)明显高于初治组(0 38),差异有统计学意义(t=2. 54,P=0. 017)。(4)CHFR的蛋白或mRNA高表达患者完全缓解率(分别为30. 2%, 42 .4% )明显低于CHFR蛋白或mRNA低表达患者(分别为88. 6%, 85. 4% ),差异有统计学意义(均P<0. 05 )。结论 在AL患者骨髓单个核细胞中CHFR基因高表达是一个耐药标志,是影响患者对化疗敏感性的因素,其低表达可能是AL患者对化疗敏感的指标之一。

Objective To investigate the expression of mitosis checkpoint gene CHFR in adult patients with acute leukemia(AL) and its clinical significance. Methods Four ml of bone marrow was extracted from 65 AL patients, 38 males and 27 females, with the median age of 35, 43 with acute myelocytic leukemia (AML) and 22 with acute lymphocytic leukemia (ALL), 45 de novo patients and 20 recurrent patients, and 8 normal donor of allogeneic bone marrow transplantation as controls. The bone marrow mononuclear cells (BMNC) were isolated. The cell cycle was examined by flow cytometric analysis. The CHFR mRNA level in the BMNC was measured by RT-PCR. The expression of CHFR protein was detected by Western blotting in 32 of the 65 patients and 8 normal persons as control. Results (1) The levels of CHFR protein and mRNA were correlated with the cumulative percentages of cells in S phases. (2) The expression level of CHFR protein in 40.6%(13/32) of the AL patients and that of the CHFR mRNA in 60.0%(27/45) of the AL patients were both significantly lower than those of the normal controls. (3) The mean expression level of CHFR protein in the recurrent acute lymphoblastic leukemia (ALL) was 0.71, significantly higher than that of the de novo group (0.38, t =2.54, P =0.017). (4) The complete remission (CR) rates in the AL patients with high expression levels of CHFR protein and mRNA were 30.2% and 42.4% respectively, significantly lower than those in the AL patients with low expression levels (88.6% and 85.4% respectively, both P <0.05). Multivariate analysis showed that CHFR was one of the influencing factors of CR rate of AL patients. Conclusion By affecting mitotic checkpoint function, CHFR inactivation plays a key role in tumorigenesis in adult patients with acute leukemia. Moreover, the aberrant expression of CHFR appears to be a good molecular marker to predict the sensitivity of acute leukemia to chemotherapy.