Effect of Dimethyl Fumarate (DMF) on T-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL.@*METHODS@#Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours.@*RESULTS@#DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771).@*CONCLUSION@#DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.

Expression of lymphoid enhance factor 1 in chronic myeloid leukemia and its clinical significance / 白血病·淋巴瘤

Objective To analyze the mRNA expression level of lymphoid enhance factor 1 (LEF-1), and to investigate its clinical significance in bone marrow mononuclear cells of patients with chronic myeloid leukemia chronic-phase (CML-CP) after initial diagnosis and chemotherapy, and to analyze its clinical significance. Methods The real-time fluorescence quantitative polymerase chain reaction was used to measure the expression level of LEF-1 gene in 38 CML-CP patients after initial diagnosis and chemotherapy and 20 persons without blood system diseases and neoplastic diseases as normal control. The difference of LEF-1 expression level between the patients and healthy control was compared, and the effect of imatinib on the main molecular response (MMR) was analyzed. Results The expression of LEF-1 mRNA in 38 newly diagnosed patients [0.00214 (0.00020 - 0.02120)] was significantly higher than that in normal controls [0.00101 (0.00009 - 0.00233)] (U= 163.0, P 0.05). The level of LEF-1 mRNA expression of non-MMR group was also higher than that of the normal control group (U= 14.0, P<0.01). The rate of acquiring MMR was significantly higher in high LEF-1 mRNA expression group [84.2 %(16/19)] than that in low expression group [47.4%(9/19)] (χ2=4.209, P<0.01). The time of acquiring MMR was significantly shorter in the high LEF-1 mRNA expression group [(10.0 ± 4.5) months] than that in the low expression group [(14.6 ± 3.8) months] (t= 2.705, P< 0.01). Conclusions LEF-1 may be involved in the occurrence and development of CML, and reflects the tumor burden. It may be one of the indicators to predict the efficacy of imatinib.

Research progress in heterogeneity of human CD4(+)FOXP3(+)T cells / 中国实验血液学杂志

It is now established that CD4(+)CD25(+)regulatory T (Treg) cells expressing transcription factor FOXP3, a regulatory subpopulation of T cells, is indispensable for the maintenance of immunological self-tolerance and immune homeostasis. FOXP3 expression in Treg cells is specific and it is the key control factor for the development, activation and function of Treg cells. At present, CD4(+)FOXP3(+)T lymphocytes are often used to define Treg cells for scientific research. But recent studies show that human CD4(+)FOXP3(+)T cells are phenotypically and functionally heterogeneous, including suppressive and non suppressive T cells. The different functions of these cell subsets can be distinguished by phenotypic differences. This review discusses the recent research progress about phenotypic characteristics and functional heterogeneity of CD4(+)FOXP3(+)T cell subsets.