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Effect of PDK1 on Notch1-Induced Mouse T-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志
Journal of Experimental Hematology ; (6): 637-642, 2016.
Article in Chinese | WPRIM | ID: wpr-360033
ABSTRACT
<p><b>OBJECTIVE</b>To explore the role of PDK1 in T-ALL development through establishing the Notch1-induced T-ALL mouse model by using Mx1-cre; LoxP system to knock-out PDK1.</p><p><b>METHODS</b>Cell cycle and apoptosis of leukemic cells were detected by flow cytometry, and relative expression of tumor-related genes and transcription factors of leukemic cells were determined by quantitative real-time PCR.</p><p><b>RESULTS</b>Notch1-induced T-ALL mouse model with inducible knock-out of PDK1 was established successfully. Compared to T-ALL control mouse model, PDK1 knock-out mice showed a significant longer survival time (P<0.01). There was no difference of cell cycle between control and PDK1 knock-out mice, and the apoptosis rate of leukemic cells in PDK1 knock-out mice was higher than that of control mice (P<0.001). PDK1 knock-out resulted in decreased expression of tumor-related genes and transcription factors, such as c-Myc and NF-κB (P<0.01), and increased expression level of P53 (P<0.01).</p><p><b>CONCLUSION</b>PDK1 knock-out can inhibit the development of T-ALL, and its mechanism may be the leukemia progression inhibited by regulating the apoptosis and expression of multiple related genes and transcription factors.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Gene Expression Regulation, Leukemic / Cell Cycle / NF-kappa B / Tumor Suppressor Protein p53 / Proto-Oncogene Proteins c-myc / Protein Serine-Threonine Kinases / Apoptosis / Mice, Knockout / Disease Models, Animal / Receptor, Notch1 Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Journal of Experimental Hematology Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Gene Expression Regulation, Leukemic / Cell Cycle / NF-kappa B / Tumor Suppressor Protein p53 / Proto-Oncogene Proteins c-myc / Protein Serine-Threonine Kinases / Apoptosis / Mice, Knockout / Disease Models, Animal / Receptor, Notch1 Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Journal of Experimental Hematology Year: 2016 Type: Article