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Background leukemia (leukemia) is a heterogeneous group of hematopoietic stem / progenitor cell differentiation block apoptosis obstacles and malignant proliferation caused hematopoietic malignancies. The incidence rate of leukemia in China 3-4/10 million in a variety of cancer mortality, leukemia in men and women were ranked sixth and eighth in the first place, in children and in adults 35 years of age. Angiogenesis on the basis of the existing vascular bed to grow new capillaries, vascular endothelial growth factor (VEGF) and its receptor is an important factor to promote tumor angiogenesis, important progress and poor prognosis of leukemia impact. Recent studies have found that the Notch signaling pathway plays an important role not only in maintaining the body's normal hematopoietic function, and some closely related to the occurrence of leukemia. Notch signaling pathway and malignant tumors of the relationship was first associated with t (7; 9) human acute T lymphoblastic leukemia (T-cell acute lymphocytic leukemia, T-ALL) is found, the latest studies have shown that acute B lymphoblastic leukemia ( B-cell acute lymphocytic leukemia, B-ALL), acute myeloid leukemia (acute myeloid leukemia, AML), multiple myeloma (multiple myeloma, MM) exist notch abnormal expression of the receptor, the Notch signaling pathway in acute leukemia in specific pathogenesis needs to be further clarified. Numerous studies exist the VEGF and Dll4/Notch signaling pathway is abnormally activated, there is some connection between the signaling pathways of VEGF and Dll4/Notch in pending further study, but the specific mechanism of action and interaction in patients with acute leukemia bone marrow microenvironment. By detecting the expression of peripheral blood mononuclear cells of Notch1, of Notch1-IC of Dll4 and Hes1 mRNA levels and protein levels in patients with acute leukemia, and to explore the role of the Notch signaling pathway genes in the pathogenesis of acute leukemia; detection of acute leukemia patients with peripheral blood mononuclear cells of VEGF, VEGFR1, VEGFR2, of Notch1 and Dll4 gene expression, explore of VEGF and Dll4/Notch signaling pathway related genes in regulating role in acute leukemia bone marrow microenvironment in angiogenesis and interrelated; thus further revealing specific pathogenesis of acute leukemia and its relationship angiogenesis disease molecular targeted therapy laboratory infrastructure. Methods: Study subjects: the main object of study in 70 patients with acute leukemia, is divided into the newly diagnosed group and complete remission group (CR), and 24 healthy volunteers served as controls. 2. Collect the object of study and control group in peripheral blood mononuclear cells (PBMNC) Immunocytochemistry, Western Blot peripheral blood mononuclear cells in patients with acute leukemia and control group Notch1-IC, Dll4 Hes1 gene protein level detection, β-actin as an internal reference. The application of real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) of peripheral blood mononuclear cells, VEGF, VEGFR1, VEGFR2, Notch1, Dll4 the Hes1 gene mRNA level detection, and β-actin as an internal reference. 3 application SPSS13.0 statistical software processing data, count data are expressed as mean ± SD, median M reaction of central tendency, Wilcoxon rank sum test and Spearman rank correlation analysis data were compared between groups, differences and related analysis, P <0.05 was considered statistically significant. Experimental results. Patients with newly diagnosed AL peripheral blood mononuclear cells of Notch1-IC of Dll4, Hes1 protein levels significantly higher than those in the control group (P <0.05). 2.CR group of Notch1-IC of Dll4, Hes1 protein expression decreased, still higher, but the difference was not statistically significant. Patients with newly diagnosed AL peripheral blood mononuclear cells VEGFR2 of Notch1, of Dll4 mRNA expression was significantly higher, VEGF higher than that of the control group, but the difference was not statistically significant 4.CR group VEGFR2 of Notch1, of Dll4 mRNA expression decreased, still high in the control group, but the difference was not statistically significant. 5. Notch1 and VEGF in the control group was significantly positive correlation of Notch1 was negatively correlated with VEGFR2; the diagnosis group Notch1 was positively correlated with VEGFR2 of Dll4 was positively correlated with VEGFR2; CR group Notch1, Dll4 and VEGFR2 no significant correlation. Both in the control group, diagnosis group CR group, Notch1, of Dll4 and VEGFR1 showed a significant positive correlation: control group Notch1 VEGFR1 positively related to the newly diagnosed group positively correlated of Dll4 with the VEGFR1 Notch1, Dll4 and VEGFR1 CR group were positively correlated . Conclusion 1. Patients with acute leukemia, abnormal activation of the Notch signaling pathway, showed upregulation of Notch1, Notch1-IC, Dll4 and Hes1, and their expression levels with disease state, suggesting that the Notch signaling pathway may play in the development of acute leukemia certain role. Relative to normal, complete remission AL patients still abnormal activation of the Notch signaling pathway. The 2.VEGF and Dll4/Notch signal path is a signal of positive and negative regulation of angiogenesis. Abnormal activation exist of VEGF and Dll4/Notch signaling pathway in patients with acute leukemia, manifested as VEGF, VEGFR2, and upregulation of Notch1 and Dll4, VEGFR2 upregulation. Normal physiological conditions, VEGF raised Notch1 expression, Notch1 inhibit the expression of VEGFR2, both interrelated and co-regulation of angiogenesis. The the abnormal pathological state, newly diagnosed the AL patients VEGFR2/VEGF with Dll4/Notch of path Collaborative enhanced expression of the two interrelated and jointly participate in the regulation of acute leukemia bone marrow microenvironment neovascularization generation. Complete remission AL patients still exists of VEGF and Dll4/Notch signal abnormal activation. Feedback effect 4.Dll4/Notch on VEGF signaling pathway may not be limited to the regulation of expression of VEGFR2, also involved in the regulation of VEGFR1 positive.
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