Expression of DNMT gene in bone marrow of patients with acute myelogenous leukemia and its significance / 中国实验血液学杂志

This study was aimed to explore the expression and significance of DNMT1 gene in bone marrow of patients with acute myelogenous leukemia (AML). The expression of DNMT1 gene was detected by real-time PCR in 30 healthy people and 126 AML patients. The results showed that the expression level of DNMT1 gene was lower in the 30 healthy people and was higher in AML patients. There was a marked decline in the expression level of DNMT1 gene after complete remission (CR) as compared with the initial treatment. The expression level of DNMT1 gene did not correlated with age, sex and the clinical characteristics at initial diagnosis such as white blood cell count and chromosomal karyotype in AML patients. The CR rate in AML patients with low expression level of DNMT1 gene was lower than that in those with high expression level. It is concluded that bone marrow DNMT1 gene level may play an important role in AML pathogenesis and can serve as an index in evaluating AML prognosis.

A retrospective study of chronic myelocytic leukemia treatment with imatinib and interferon-α / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of chronic myelocytic leukemia (CML) patients treated with imatinib (IM) and interferon (IFN)-α.</p><p><b>METHODS</b>One hundred and fifty five CML patients at chronic phase were included in the study. All patients were divided into two groups according to treatment regimen: IM + IFN group and IM group. Complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate, complete molecular response (CMR) rate, overall survival (OS) and progression free survival (PFS) were observed and compared in both groups.</p><p><b>RESULTS</b>The CCyR rate was higher in the IM + IFN group than that in the IM group at 6 months (60.6% vs 41.6%, P < 0.05), but no difference was observed later on. The MMR + CMR rate was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (71.2% vs 34.8%, 77.3% vs 52.8%, respectively, P < 0.05), but no difference after that. After stratification according to Sokal risk, the CCyR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months (77.8% vs 52.6%, 75.0% vs 46.7%, P < 0.05), but not from 12 months on; the MMR + CMR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (85.2% vs 36.8%, 90.0% vs 36.7%, P < 0.05; 88.9% vs 57.9%, 90.0% vs 56.7%, P < 0.05), but not from 24 months on. There was no significant difference in high-risk patients. OS in IM and IM + IFN group at 6, 12, 24 and 36 months was 100%, 100%, 96.8% and 90.0%, and 100%, 100%, 97.9% and 93.1%, respectively. PFS in IM and IM + IFN group at 6, 12, 24 and 36 months was 97.8%, 95.5%, 91.9% and 85.5%, and 98.5%, 95.5%, 91.5% and 86.2%, respectively. There was no significant difference in OS (u = 0.427, P = 0.514) or PFS (u = 0.556, P = 0.456). The side effects in both groups included pancytopenia, edema, weight gain, ostalgia, rash and muscle spasm. In addition, patients in the IM + IFN group suffered from flu-like symptoms, impaired liver function, abnormal thyroid function and extremity sensory disturbance. It seemed that grade III or IV pancytopenia occurred more commonly in the patients in the IM + IFN group, however, there was no statistically significance.</p><p><b>CONCLUSIONS</b>The response to IM + IFN is more rapid than that to IM alone, especially for the low- and intermediate-risk patients. It seems no benefit of the addition of IFN to treatment of high-risk patients. During the period of 36 months, survival rate in the IM + IFN group is not higher than that in IM group, and it is possible to increase the side effects of pharmaceutical drugs.</p>

Effect of bortezomib on acute graft-versus-host disease in mice model and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of bortezomib on prophylaxis of acute graft-versus-host disease (aGVHD) after mouse allogeneic-bone marrow transplantation (allo-BMT) and its mechanism.</p><p><b>METHODS</b>C57BL/6 (H-2(b)) mice were used as donors and BALB/c (H-2d+) mice as recipients. After allo-BMT, the BALB/c mice were divided into 3 groups, ie. group A:BMT control, group B: BMT + early infusion of bortezomib (1 mg kg(-1) d(-1), day 0-3), group C: BMT + late infusion of bortezomib (1 mg kg(-1) d(-1), day 5-7). Clinical manifestations of aGVHD, pathohistological changes, survival rate and levels of recipients H-2(b) cells detected by flow cytometry in the recipient mice were observed. Monodirectional mixed lymphocyte culture (MLC) system was established ex vivo and different concentrations of bortezomib (0, 2, 4, 8 nmol/L) were added to the system. The viability of the cells was detected by CCK-8 assay and cells apoptosis by flow cytometry. The concentrations of IL-2, IFN-gamma, TNF-alpha in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The mice in group A developed typical aGVHD and all died of aGVHD within 3 weeks after transplantation, with a median survival time of (16.1 +/- 2.5) d. The symptoms of aGVHD was milder in group B than in group A, and the median survival time was significantly longer. The 60-day survival rate in group B was 70%, being significantly higher than that in other two groups(P<0.05). The mean value of donor-derived cell (H-2(b) cells) in group B was (98.1 +/- 1.1)% at 60 days. The symptoms of aGVHD was significantly severer in group C than in group A, and the median survival time was shorter. Bortezomib inhibited the cells viability in MLC system in a dose-dependent manner. After treated with 8 nmol/L bortezomib for 24 h, the inhibition ratio of cells viability was (41.4 +/- 6.0)%. The cell apoptosis rate increased gradually with bortezomib treatment for 12 h, 24 h and 36 h. After treated with 8 nmol/L bortezomib for 36 h, the apoptosis rate was (62.8 +/- 7.0)%. After treated for 24 h, the levels of IL-2, IFN-gamma and TNF-alpha in the supernatant were decreased.</p><p><b>CONCLUSIONS</b>Bortezomib administered immediately after allogeneic BMT can prevent aGVHD, improve the survival rate and have no influence of engraftment in the recipient mice. Delayed administration of bortezomib results in acceleration of aGVHD-induced mortality. Its mechanism maybe inhibition of the lymphocyte viability, increase of the cells apoptosis rate, and inhibition of secretion of IL-2, IFN-gamma, and TNF-alpha.</p>