Effects of Decitabine Combined with Bortezomib on the Proliferation of Mantle Cell Lymphoma Cell Lines and Its Underling Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.@*METHODS@#Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.@*RESULTS@#Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.@*CONCLUSION@#The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.

Expression of c-fes gene in leukemia cells and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the expression of c-fes gene in leukemia patients and its clinical significance. The expression of c-fes mRNA in bone marrow cells from 121 cases of acute and chronic leukemia patients, and the expression of c-fes mRNA in peripheral blood mononuclear cells of 20 normal persons were detected by real time-quantitative reverse transcription polymerase chain reaction (RQ-PCR). The results showed that the level of c-fes mRNA in AML patients was higher than that in normal controls [(48.017 +/- 57.170) x 10(-3) vs (0.152 +/- 0.398) x 10(-3)] (p < 0.0001); but there was no significant differences of level of c-fes mRNA between samples of ALL and normal controls(0.047 +/- 0.068) x 10(-3) vs(0.152 +/- 0.398) x 10(-3) (p>0.05); the level of c-fes mRNA in CML patients was higher than that in normal persons (21.605 +/- 24.818) x 10(-3) vs (0.152 +/- 0.398) x 10(-3) (p < 0.0001). The positive expression rate of c-fes gene in CML-CP patients (80%) was higher than that in CML-AP patients (66.7%) and CML-BP (28.6%) patients. In AML patients, c-fes gene was expressed higher in M(2) (80.77%) and M(3) (92.86%) patients. The remission rate of AML (except M(3))patients who had expression of c-fes gene was 81.08%, which was higher than that of patients with no expression of c-fes gene (40.00%). It is concluded that c-fes gene expression was found in myeloid leukemias, whereas low or no expression in lymphocytic leukemias. The differentiation of myelocytic cells may be related to c-fes gene. All AML (except M(3))patients with high level of c-fes mRNA may get good prognosis.

Expression and significance of X-linked inhibitor of apoptosis protein and its antagonized proteins in acute leukemia / 中国实验血液学杂志

To investigate the expression and significance of X-linked inhibitor of apoptosis protein (XIAP) and XIAP-associated factor 1 (XAF1) in acute leukemia, the expression of XIAP, XAF1, Smac, and HtrA2 mRNA in the bone marrow aspirates from 87 newly diagnosed AL patients, 23 patients in remission, 6 patients in relapse, and 17 normal controls were detected by means of reverse transcriptase polymerase chain reaction (RT-PCR), and their relationship with clinical therapeutic efficiency was analyzed. The results showed that the expression level of XIAP mRNA in newly diagnosed AL patients (0.990 +/- 0.337) was significantly higher than that in normal controls (0.395 +/- 0.148) (P < 0.01); the positive rate and expression level of XAF1 mRNA in newly diagnosed AL patients (56.32%, 0.246 +/- 0.267) were significantly lower than that in normal controls (100%, 0.964 +/- 0.387) (P < 0.01). In 69 out of 87 newly diagnosed AL patients, efficacy remained evaluable. AL patients with high level of XIAP achieved a lower complete remission (CR) rate than patients with low level of XIAP (54.55% and 86.11%, respectively) (P < 0.01). XAF1 positive patients achieved a higher CR rate than XAF1 negative patients (86.84% and 51.61%, respectively) (P < 0.01). It is concluded that the overexpression of XIAP and negativity of XAF1 may be two adverse prognostic factors in AL patients.

Relationship between resistance to chemotherapy and expression of breast cancer resistance protein (BCRP) gene in patients with acute leukemia / 中国实验血液学杂志

In order to investigate the relationship between the expression of breast cancer resistance protein (BCRP) gene and drug resistance in patients with acute leukemia (AL), semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of BCRP mRNA in AL patients and 15 normal subjects. Beta(2)-microglobin (beta(2)-MG) was used as positive reference. BCRP/beta(2)-MG ratio >or= 0.5 was defined as BCRP mRNA positive. The results showed that the positive percentage of BCRP gene expression in newly diagnosed group was 37.6%. The first complete remission rate was 79.3% and 31.6% in BCRP mRNA negative and BCRP mRNA positive patients respectively. The difference was significant (P = 0.001). The expression levels of BCRP mRNA in drug resistance group and drug sensitive group were 0.962 +/- 0.426 and 0.315 +/- 0.296 respectively (P = 0.0001). The expression level of BCRP mRNA in relapsed/refractory group was significantly higher than that in newly diagnosed group (P = 0.0025). The expression level of BCRP gene in normal individuals and long-term survival group was very low and correlated with FAB subtypes. It is concluded that high expression of BCRP mRNA leads to clinical drug resistance and is an unfavorable factor for prognosis of AL patients except acute promyelocytic leukemia.