Changes Of Gene Expression Profile Of TGF-β And Its Signal Transduction Pathway Of Acute Leukemia Cells

Acute leukemia (AL) is a clone disorder that characterized by haemopoietic stem cells malignancy proliferative. Transforming growth factor-β1 (TGF-β1) is the most powerful negatively regulation autocrine agent that can control blood cells multiplication. Either discrepancy of activation and/or expression profiles of TGF-βor impairment of expression profiles of TGF-βreceptor and/or post expression profiles of TGF-βreceptor can vanish growth inhibiting action that make blood cells malignant multiplication. Many investigations acquire that leukemic cell proliferation can be blanketed and apoptosis of leukemic cells can be induced after exogenous TGF-β1 admoved. Our protophase research detect that TGF-β1 levels in patients serum of acute leukemia are manifest lower than TGF-β1 levels in patients serum of normal. Workover reportor of national cancer institute findings that absence of Smad3 proteinum were occurrence in children acute T Lymphocytic leukemia suffereres, then result in anomalism in gene expression profiles of TGF-βsignal transduaction pathway, that make important role in invasion of children acute T Lymphocytic leukemia .Thus the present study included three sections, aimed at investigating the gene expression profiles of TGF-βsignal transduaction pathway of acute lymphocytic leukemia B and acute myelocytic leukemia and acute myelocytic leukemia after induced by As2O3,then study expression profiles of TGF-β1 of acute leukemia after induced by AS-PS-ODNS of genes changed in gene expression profiles of TGF-βsignal transduction pathway of acute leukemia. The findings of research is presented as follows:In the part one, the B-ALL cells, AML cells were detected by using the real time RT-PCR and the level of TGF-β1mRNA was obviously reduced compared with the normal figure. TGF-β/BMP signal transduction pathway related gene chip was used to detect the level of signal transduction pathway related gene of B-ALL cells, screening up-regulation gene MYC, Smad1 and down regulation gene IL6, Smad7; the TGF-βsignal transduction pathway related gene of AML cells was detected and down regulation gene IL6, Smad7 was screened.In the part two, the real time RT-PCR was used to measure HL-60 cells and NB4 cells induced by As2O3, and it was found that TGF-β1mRNA was obviously raised compared with the normal figure. TGF-β/BMP signal transduction pathway related gene chip was used to detect the displayed level of the TGF-βsignal transduction pathway of HL-60 cells and NB4 cells before and after which were induced by As2O3. The obviously-increased gene IL6, Smad7 and reduced gene MYC was screened in the induced HL-60 cells and NB4 cells.In the part three, the gene AS- PS-ODN of MYC and Smad1 were used to intervene NALM6 cells and Raji cells, whose level of TGF-β1mRNA rose 24 hours later. NALM6 cells and Raji cells co-cultured by AS- PS-ODN of Smad1,MYC were capable of apoptosis, repressing, inducing and polarizing NALM6 cells and Raji cells.To conclusion, the gene expression profile of TGF-βsignal transduction pathway exist abnomal in acute leukemia, probably in acute leukemia while that of IL6, Smad7 mRNA was down-regulationed and MYC, Smad1 mRNA was up- regulationed. These genes may be can modulate TGF-βsignal transduction pathway.