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Pathogenesis and Treatment Strategies of T Cell Acute Lymphoma Leukemia

Author: YangYanPing
Tutor: WangGuanJun
School: Jilin University
Course: Internal Medicine
Keywords: Notch1 T cell leukemia CD25 NK cells IFN-γ
CLC: R733.7
Type: PhD thesis
Year: 2009
Downloads: 143
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Acute lymphoblastic leukemia (ALL) in all leukemia accounted for 12%, while T-cell acute lymphoblastic leukemia (T-ALL): 15% of children with ALL, accounting for 25% of adult ALL. Through chemotherapy, hematopoietic stem cell transplantation, there are still 20-25% of children develop into a poor prognosis refractory leukemia and adult patients, the 3-year survival rate is only 35-40%. Andrew et al in 2004 first proposed more than 50% of human T-ALL activation of Notch1 mutant Therefore Notch1 become recognized the pathogenesis of T-ALL oncogenes. Explore the relationship between Notch1 and T-ALL pathogenesis will further guide the clinical treatment of T-ALL. Pathogenesis: Notch1 transduction of T-ALL leukemia cells in mice subculture, closer to the clinical phenotype and functional T-ALL model was established for the first time. Phenotype characterized by expression of CD 4 , part of the expression of CD25, highly TCRVβ8.1/8.2 rearrangement, low expression of MHCI. Its features: not survive under normal culture conditions in vitro, but can survive under ConA or rhIL-2 conditions. This study is the first Notch1-transduced T-ALL leukemia cells are divided into different expression levels of CD25, CD25 and CD25-2 class of cells in normal mice in vivo distribution in these two types of cells and caused mortality fewer CD25-cells infiltrating the spleen and lymph nodes, with faster mortality. CD25 cells can be converted into CD25-cells, CD25-cells into CD25 cells rarely, but in vitro rhIL-2 cultured under the conditions, the CD25-Notch was able to complete transformation into CD25 cells. EL4 lymphoma cell lines further evidence of the CD25-cells with faster mortality CD25 EL4 EL4 in Multi Power in the body can differentiate into CD25-CD25-the EL4 EL4 in Multi Power can not differentiate into CD25's. Therapeutic strategy: The study was first proposed in vivo tests, syngeneic NK cells after removal of the survival of leukemic mice was significantly shorter, and the CD25 cell lethal rate faster than the lethality rate of the CD25-cells, CD25-cells are able to differentiate CD25 cells. Normal NK cells, anti-CD25 leukemic cells, inhibition of CD25-leukemia cells to CD25 changes. The same time be able to reduce the CD25 tumors lethality. Allogeneic hematopoietic stem cell transplantation can improve the leukemia survival time. IFN-γ can not through its receptors play an indirect role in killing tumor.

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