title: [Effect of PDK1 on Notch1-Induced Mouse T-cell Acute Lymphoblastic Leukemia].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Hu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Hui-Dong
authors.initials: HD
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 30020, China. E-mail: wpyuan@ihcams.ac.cn.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C489428:Myc protein, mouse; D016328:NF-kappa B; C497762:Notch1 protein, mouse; C000631433:Pdk1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051881:Receptor, Notch1; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases