| Background and Objective:Acute leukemia, a clonal disorder of hematopoietic stem cells, is the most common form of hematologic malignancies characterized by the appearance of increased numbers of immature leukemic cells in the marrow. The occurrence and development of tumor is the result of the interaction of long-term, multi-factor, multi-stage and multi-gene changes. The activation of oncogenes and inactivation of tumor suppressor genes plays a central role in the pathogenesis of malignant diseases. Transforming growth factor-β(TGF-β) is a kind of cytokine which plays an important role in the regulation of resting, proliferation and differentiation of human hematopoietic stem/progenitor cells. Furthermore, it has been reported that TGF-β1 was expressed in acute leukemia with controversial clinical significances. DPC4, deleted in pancreatic cancer locus4, is a kind of tumor suppressor gene and encodes protein Smad4 which belongs to the superfamily of transforming growth factor. Morerover, as the only substrate of TGF-β1, Smad4 is involved in the signaling pathway of TGF-β1. It has been evidenced that Smad4 had a lower expression level in cancers of stomac, colon, thyroid, liver etc. and apart from hepatocarcinoma, its expression were negatively correlated to the expression of TGF-β1. But little reports documented the expression of Smad4 in leukemia. In order to investigate the mechanism of leukemic transformation and infiltration, immunocytochemical staining was performed to examine the expression of TGF-β1 and Smad4 in bone marrow mononuclear cells from AL patients and their relationship was analyzed.Materials and Methods:1. All the samples were obtained from the patients of the department of hematology in the First Affiliated Hospital of Zhengzhou University through February of 2009 to August of 2009. All patients were divided into 4 groups:①De novo leukemia group (n=55):AML (n=34), ALL (n=19).②AL-CR group:bone marrow samples from patients (n=21) who reached CR after chemotherapy.③The control group:bone marrow samples from non-maligant hematological diseases (n=16).2. Collecting the bone marrow mononuclear cells of all samples, the expression of TGF-β1 and Smad4 were detected by immunocytochemical staining.3. The results were analyzed with chi-square test by SPSS 17.0 andα=0.05 was considered to be statistically significant.Results:1. The positive rate of TGF-β1 was 80.56% in de novo AML,78.95% in de novo ALL, 66.67% in AL-CR and 68.75% in the control group. No statistical significances were found as to the expression of TGF-β1 between different two groups.2. The positive rate of Smad4 in de novo AML, ALL, AL-CR and the control was 30.56%,68.42%,71.43% and 75% respectively. The expression of Smad4 in AML was significantly lower than that in ALL,AL-CR, the control groups (P<0.05). There was no significant difference between the positive rate of ALL and AL-CR, ALL and the control (P>0.05). 3. No significant correlation between TGF-β1and Smad4 in AL were found (rs=0.076, P>0.05)4. The expression of Smad4 was positively correlated to leukemic infiltration (P< 0.05). There was no significant relationship between TGF-β1 expression and clinical features (P>0.05)Conclusions:1. There was no significant difference of TGF-β1 expression between De novo leukemia and control, suggesting that there was no obvious difference between acute leukemia cell and the control in the ability of TGF-β1 synthesis.2. The expression of Smad4 in AML was significantly lower than that in control, whereas there was no obvious difference between ALL and control indicating that Smad4 may be related to the occurance of AML.
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