Expression of mitosis checkpoint gene CHFR in acute leukemia

Abstract

To investigate the expression of mitosis checkpoint gene CHFR in adult patients with acute leukemia (AL) and its clinical significance. 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. (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. 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.