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Expression And Correlation Research Of CDX2 And Wnt/β-catenin In Children's Acute Leukemia

Posted on:2012-12-20Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2214330338456904Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Acute leukemia, acute leukemia (AL) is a kind of hematopoietic system of the affected malignant proliferating disease, some factors leading to the blood system proliferating out of control and apoptosis way, triggering leukemia cells stuck, and accumulated proliferative suppressed normal hematopoiesis cell proliferation.Many factors and multiple genes in this disease occurrence and development is a complicated process, at present the specific pathogenesis is still study is unknown. More experimental research proof various protocarcinogenic gene, tumor-suppressor genes and cancer gene in expression function abnormality or loss, cause malignant cell proliferation, differentiation and apoptosis of path by block.Caudal type homologous box CDX2 (caudal gene transcription, those factor2 homeobox CDX2) genes and proteins, in 1987 Mlodzik research black abdomen drosophila homologous special-shaped mutations in separation of success. In recent years, in the human chromosomes research proof, CDX2 gene is a protocarcinogenic gene, the span of 22kb, located in 13 chromosome q12-13, consists of two intron and three explicit son constitute, its downstream CDX2 proteins expressed through spiraling - loops - spiral form and the corresponding areas of DNA combination, total contains a single amino acid, as 311 DNA transcription factor to control the expression. In mice, and the period of maturity and embryonic development period found that in the early embryo most CDX2 exists in neural tube and three mesoderm to induce embryonic before and after the formation of polarity, cell differentiation and the consistency of the organ happening. Embryo development gradually in small intestine cells expressed inducing differentiation intestinal cells. In mice CDX2 adulthood, in all of the colonic epithelium cells and the small intestine villi epithelial cells express, and have been stable distributions. An immune to human epithelial cells and organized research found that CDX2 in normal adults and human embryo distribution rule and mice are similar. From people of the development of embryos eighth week, can be detected in the fetus CDX2 expressed in gastrointestinal tract, in adult the mutation epithelial cells, CDX2 exists in pancreatic ducts and acini epithelial cells derived from the endoderm intestinal epithelium and gastric mucosa, but in normal epithelial cells and esophagus cells without express, in addition to the digestive system outside the other system normal epithelial were not found CDX2 existence. But in some tumor cells found CDX2's expression of abnormalities. Foreign documents, reported in 90% of the patients with acute myelogenous leukemia (aml) mononuclear cells found in CDX2 over-expressed in leukemia cell. Scholl etc through to acute mononuclear leukemia after the pathogenesis of research, CDX2 genes in malignant confirmed haematology expressed in the abnormal exists generally, common effect gene transduction pathways in the role of CDX2 is self-renewal potential and promote hemopoietic myelogenous proliferation. Acute leukemia mononuclear cells in CDX2 can also HOX gene expression of a role. Rawat research rat myelogenous found after CDX2 component type, such as leukemia HOX gene expression leads to HOXaP and HOXbP express abnormalities. Normal karyotype of acute leukemia sufferer mononuclear cells CDX2 expression and existing chromosome translocation if t (8;21) and t (15;17) patients CDX2 express quantity, in comparison, and increased levels of 14 times HOX gene expression of decline.Beta-catenin is a protocarcinogenic gene, located in human chromosomes 3p21. 3,23.2 KB,downstream coding the molecular weight of 92 and 103 beta catenin protein. This has a variety of functions of the cytoskeleton protein can not only with E - calcium sticky protein function make the same type of adhesion in cancer cells, the transfer and infestations, more can play an important role as Wnt/beta catenin cell-to-cell signaling pathways important signal molecules participate in abnormal cellular proliferation, embryonic development and tumor formation. The normal human catenin expression in beta in cell membranes, and exercise between cells adhesion ability. In tumor cells beta catenin in nuclei and cytoplasm differentially expressed, causing abnormal Wnt signaling pathways activate downstream gene c-cyclinD1, myc, in tumors progress plays an important role.Objective:this paper by analyzing in children with leukaemia bone marrow cells hropoietin drosophila homologous alien box transcription factors CDX2 genes and proteins of quantitative determination, beta connexins (beta) genes and proteins catenin expression, analyzed the correlation, explore and CDX2 Wnt/beta catenin in childhood leukemia on mechanism of interaction and clinical use value.Methods:through real-time fluorescence semi-quantitative RT-PCR and enzyme-linked immunosorbent adsorption method (Elisa) test children with acute B lymphocytes leukemia (ALL) B-56 cases with acute T lymphocytes leukemia (T-ALL) in 12 cases, acute myeloid cells leukemia (AML) 22 cases of bone marrow cells and hropoietin children in serum CDX2 and beta catenin (CTNNB) genes and protein expression level, and compared with the 13 cases of children with leukemia compared with (CON), analysis CDX2 mRNA and beta catenin expression in children with acute leukemia in clinical outcomes, and analyzes the relationship CDX2 gene and protein.Results:1. The acute leukemia CDX2 mRNA expression level of children's obviously higher than the leukemia patients (P<0.01). ALL the children CDX2 mRNA expression level higher than AML patients (P<0.05).56 cases with complete remission, completely catabatic cases (CR) group ALL CDX2 mRNA expression of children's lowest, close to the children with leukemia group (P<0.01). B cells ALL (B - ALL) of children's CDX2 expression above T cells ALL (T - ALL), its differences are statistically significant (P<0.01). And CDX2 expression level of children's AML higher than that of normal control group, was statistically significant (P>0.05).2. Beta-catenin in acute leukemic patients expression is obviously higher than the children leukaemia (P<0.01). Both groups ALL children beta catenin expression level higher than AML patients (P< 0.05), ALL completely catabatic cases (complete remission, CR) groups of children's beta catenin express lowest, close to the children with leukemia group (P< 0.05). B cells ALL (B-ALL) of children's beta catenin expression above T cells ALL (T-ALL), its differences are statistically significant (P <0.01).3. CDX2 in childhood leukemia each protein in the quantitative and gene expression quantity has correlation, a statistically significant (P< 0.05).4. CDX2 and beta catenin in childhood leukemia each first group has significant correlation (P<0.01).Conclusions:1. The children with acute leukemia cell in the bone marrow hropoietin CDX2 and beta-catenin abnormally high expression, they may be involved in the children with acute leukemia, can the onset of the diagnosis and targets of leukemia treatment play an important role.2. CDX2 protein in CDX2 genes are associated with CDX2 proteins can be, indicating the acute leukemia collaborative or simplified detection.3. In children with acute leukemia various group, CDX2 and beta-catenin relevance, tip leukemia developing both synergistic.4. In different types of children with acute leukemia, B - ALL positive express the highest rate, T - ALL positive expression rate lowest, indicate different types of leukemia pathogenesis each are not identical, need to progress research.
Keywords/Search Tags:Children, Leukemia, RT-PCR, ELISA, CDX2, Beta-catenin
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