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The Prognosis and Mechanism of Leukemia Stem Cell on Childhood Acute Lymphoblastic Leukemia

Author: LongJuan
Tutor: TuZhiGuang
School: Chongqing Medical University
Course: Clinical Laboratory Science
Keywords: Leukemia stem cells Child Acute lymphoblastic leukemia Prognosis Mechanism
CLC: R733.7
Type: Master's thesis
Year: 2011
Downloads: 36
Quote: 0
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Abstract


Objective: sorting, identification of children with acute lymphoblastic leukemia stem cells, the establishment of leukemia stem cells / NOD-SCID mouse leukemia model, observe the mice survival, and analysis of leukemia stem cells and clinical features and prognosis of acute lymphoblastic relationship; research beta-arrestin1 as well as the related gene expression in the leukemia stem cells, to explore the pathogenesis of acute lymphoblastic leukemia stem cells affect experimental basis, looking for children acute lymphoblastic therapy target. Methods: sorting by magnetic activated cell sorting method, flow cytometry analysis, RT-PCR and fluorescence in situ hybridization identification of acute lymphoblastic leukemia stem cells in the bone marrow of children and the group irradiated cells were injected via the tail vein The NOD-SCID mice, murine leukemia model. Detected by flow cytometry in the bone marrow of children with acute lymphoblastic leukemia stem cell surface marker CD34 to CD38 to - the expression of cell acute lymphoblastic leukemia stem cell surface markers of clinical features and prognosis of leukemia in mice using the established model validation of the group cell acute lymphocytic leukemia prognosis. Using real-time RT-PCR, immunofluorescence, immunohistochemistry to detect beta-arrestin1 in the bone marrow of patients sub-mRNA and protein expression levels of selected cells and mouse bone marrow mononuclear cells, real-time RT-PCR detection of gene the expression. Results: Flow cytometry was successfully sorted CD34 ~ CD38 ~ - leukemia stem cell population, and the population of cells express the leukemia stem cells the molecular marker CD19 and acute lymphoblastic related fusion gene. Tail vein injection into NOD-SCID mice, mice peripheral blood white blood cell count was gradually increased, showing that naive cells, bone marrow was acute lymphocytic leukemia bone marrow like leukemia mouse model was successfully established. Injection of CD34 to CD38 ~ - cell populations in mice, the overall survival rate is less than CD34-CD38 group and blank control group of mice (P lt; 0.05) Detection and analysis of clinical specimens children with ALL, the expression of CD34 ~ CD38 ~ - with acute lymphoblastic prognostic factors such as age, peripheral white blood cell count, peripheral blood blasts, cytogenetic classification fusion gene, response to chemotherapy, extramedullary infiltration and risk stratification (P lt; 0.05). In addition, compared with the control group, CD34 to CD38 to - cells increased beta-arrestin1 mRNA and protein expression (P lt; 0.05); real-time RT-PCR detection of developmental gene mRNA expression and found that Wnt3a and beta -catenin in CD34 and CD38 to - cells compared with the control group, increased significantly (P lt; 0.05) to beta-catenin. Conclusion: The sub-Isolation and identification of children with acute lymphoblastic leukemia stem cells, and the establishment of the NOD-SCID mouse leukemia model, injection of CD34 ~ CD38 ~ - cell populations overall survival of the mice was significantly lower. High expression of children's clinical study found that CD34 to CD38 ~ - acute lymphocytic leukemia associated with poor prognosis. beta-arrestin1, Wnt3a and beta-catenin in CD34 - CD38 ~ - cell population was highly expressed.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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