| [Background and Objective]Leukemia is a malignant clonal disease derived from hematopoietic stem cells, and leukemia cells in the bone marrow and other tissues accumulated a large number of proliferation, and invased of other organs and tissues, so that normal hematopoiesis was inhibited. The mechanism may be related with environmental factors, viral infection, gene mutation, and other blood diseases and so on. Although the pathogenesis of leukemia is not clear, but with the progress of modern experimental methods, the people have a novel knowledge and discovery gradually. The latest study found that cell proliferation and regulation of infinite abnormality played an important role in the development of leukemia. Cell proliferation and apoptosis to maintain the balance of the organism is an important factor, if the blockage of apoptosis or uncontrolled proliferation may result in tumor formation.PDCD4 gene is regulated by apoptosis, but its exact function is unclear. Now more and more evidence showed that the gene can affect the transcription, translation and regulation of different signal transduction pathways and may also play a role in tumor suppression. TGF-β1 is a common pleiotropic cytokine, which can effectively stimulate the growth of fibroblast cells to repair wounds, but also regulate blood and inhibit tumor proliferation. Therefore, this project focuses on the PDCD4 and TGF-(β1 in acute myeloid leukemia and significance of the expression in bone marrow, and explores its role in leukemia and its possible mechanism.[Methods] The sample was collected in Department of Hematology, Qilu Hospital on 2009.8-2009.12. The sample included iron deficiency anemia (control group) 20 cases,6 males and 14 females,27 to 70 years old, an average of 39 years; patients with newly diagnosed acute myeloid leukemia (AML) 30,18 males and 12 females, 18 to 73 years, mean 46 years; complete remission patients (AML-CR) 30,16 males patients,14 females,16 to 67 years, with an average of 41 years. Patients were diagnosed by clinically, blood, bone marrow and tissue staining, immunophenotyping, chromosome diagnosis. RT-PCR, ELISA and Western blotting were three methods of gene and protein levels detected in the bone marrow mononuclear cells PDCD4, TGF-β1 expression, and analysis of the correlation between each other. SPSS13.0 software was used for statistical analysis. p<0.05 was considered statistically significant.[Results]The results of RT-PCR indicated that mRNA expression of PDCD4 and TGF-β1 in the newly diagnosed AML group was significantly lower than the control group(p <0.05),and the AML-CR group was higher than the AML group, but the difference had no significance(p>0.05).The results of ELISA showed that the level of TGF-β1 in newly diagnosed AML group was significantly lower than the other two groups(P <0.05). The results of Western blotting indicated that expression of PDCD4 protein in AML group was significantly lower than the control group and the AML-CR group(P<0.05).PDCD4,TGF-β1expression had positive correlation(p<0.05).[Conclusion]PDCD4 mRNA and protein levels were significantly lower in newly diagnosed AML, suggesting that patients with newly diagnosed AML in bone marrow cells blocked apoptosis might be involved in the development of leukemia. mRNA expression in AML-CR group was significantly higher than AML group, but not statistically significant, the sample may be less in this study,and expand the sample of the AML-CR group and AML patients may be found in AML-CR group and the AML the difference between the groups. TGF-β1mRNA and protein expression levels in newly diagnosed AML have shown a significant reduction, indicating that the bone marrow of newly diagnosed AML patients decreased production of TGF-β1, the proliferation of leukemia cells but lost a lot of growth, and the lack of TGF-β1 on the leukemia cell maturation induced differentiation and accelerated the deterioration of the condition. Therefore, detection of AML patients with levels of TGF-β1 can be used as diagnosis and prognosis of the disease one of the indicators. Newly diagnosed AML patients achieved complete remission, TGF-β1 mRNA expression, although significantly higher than that of AML group, but not statistically significant, while the expression of TGF-β1 was significantly higher than the AML group, the difference was statistically significant, may be the body cells can secrete a variety of TGF-β1, may be too small sample size of this study, whether TGF-β1 as a predictor of complete remission still need further study. Study found, PDCD4, TGF-β1 expression was positively correlated, suggesting that TGF-β1 may regulate PDCD4 expression by promoting apoptosis of leukemia cells. |
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