| Background and ObjectiveThe acute leukemia is a common malignance disease of hematopoietic system. The excessive proliferation of malignant cells infiltrates marrow and extramedullary tissue, leading to the inhibition of normal hematopoietic function and the organomegaly. The organomegaly caused by leukemic cell infiltration is a main clinical representation and served as one of the important unfavorable prognostic factors. Molecular basis on leukemic cell infiltration extramedullarily has not been elucidated. Existing data indicate that 6-catenin and matrix metalloproteinase participate in extramedullary infiltration of leukemic cells by changing leukemic cell cohesion.β-catenin is a multifunctional protein, which not only mediates cell-cell adhesion, but also acts as the key factor of Wnt/β-catenin signal transduction pathway. It promotes the proliferation and inhibits the apoptosis of tumor cells. MMP-2 and MMP-9 have been found to participate in leukemic cell infiltration of extramedullary. Matrix metalloproteinase-7 (MMP-7) is a member of matrix metalloproteinase family, which degenerate almost all components of extra cellular matrix. It has been reported that MMP-7 is related to invasion/metastasis in several solid tumors. The role of MMP-7 in malignant hematological disease has been explored in K562 cell line. However, the relationship between expression of MMP-7 and leukemic cell infiltration has not been reported. Effect of 6-catenin in hematological malignant diseases has been reported only in leukemic cell lines. Expression ofβ-catenin in primary leukemic cells has been reported in a few Chinese papers. Study on the relationship of 6-catenin and MMP-7 and clinical significance of them has not been reported. In this study, MMP-7 and 6-catenin were simultaneously detected in bone marrow mononuclear cell from patients with acute leukemia by immunocytochemical staining. Their relationship and clinical significance were explored.Materials and method1. Bone marrow sample: All the bone marrow samples were obtained from the patients of the Department of Hematology in the First Affiliated Hospital of Zhengzhou University in 2006, after patient's or family member's consent. The patients with acute leukemia were diagnosed and classified according to FAB classification, complemented by cytogenetic assay and immunophenotype of leukemic cells (MIC classification). Among them, there were 31 patients with AML and 20 with ALL. Bone marrows from patients with non-malignant diseases (n=14) were taken as control group, including 3 cases of IDA, 2 cases of megaloblastic anemia, 3 cases of ITP, 1 case of ARF and 1 case of Still disease, 4 cases of FOU.2. Detect of MMP-7 andβ-catenin: Bone marrow mononuclear cells (BMMNC) were collected on Ficoll-Hypaque (D=1.077) by centrifugation and loaded on slides to detect the expression of MMP-7 and±-catenin by immunocytochemical staining.3. The data were analyzed with t-test and Pearson correlation by SPSS10.0, size of significance test a=0.05.Results1. MMP-7 was expressed in BMMNC from acute leukemia as red-yellowish granules in cytoplasm. Positive rate and score were (45.22±18.79) % and 71.16±36.76, respectively. The expression of MMP-7 in control BMMNC was negative with a few of weak positive. Positive rate and score were (9.54±5.34) % and 12.74±7.01, respectively. Difference between leukemia group and control group was statistically significant (p<0.05) .2.β-catenin was expressed in BMMNC from acute leukemia and located in both cytoplasm and nuclear. Positive rate and score were(54.05±18.86)% and 86.29±35.04, respectively. Expression ofβ-catenin is negative in BMMNC from most of control samples with a few weak positive. Positive rate and score were (18.11±9.29) % and 18.62±9.53, respectively. Difference between leukemia group and control group was statistically significant (p<0.05) .3. There was a positive relation between the positive rates of MMP-7 andβ-catenin in acute leukemia with a correlation coefficient at 0.58.4. Positive rates of MMP-7 andβ-catenin in patients with extramedullary infiltration were (63.83±9.16) % and (66.87±14.38) %, respectively, which were significant higher than those in patients without extramedullary infiltration with positive rate at (31.30±7.29) % and (37.22±10.59) % (p<0.05) .Conclusion1. Expressions ofβ-catenin and MMP-7 in BMMNC from patients with acute leukemia were significantly higher than those in control group, which suggested that expressions ofβ-catenin and MMP-7 are abnormal in acute leukemic cells.2. There were positive relations between the expression of MMP-7 andβ-catenin in BMMNC from acute leukemia in positive rate. These data suggested that Wnt/β-catenin signal transmission pathway is abnormal activated in acute leukemia.3. Expression of MMP-7 andβ-catenin in BMMNC in patients with extramedullary infiltration was significantly higher than that in patients without extramedullary infiltration, which suggested that MMP-7 andβ-catenin might be involved in infiltration of acute leukemic cells.
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