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Leukemogenic Fusion Gene (p190 BCR-ABL) Transduction into Hematopoietic Stem/Progenitor Cells in the Common Marmoset

Leukemogenic Fusion Gene (p190 BCR-ABL) Transduction into Hematopoietic Stem/Progenitor Cells in the Common Marmoset

作     者:Yan Dong Seiichiro Kobayashi Yamin Tian Manabu Ozawa Takafumi Hiramoto Kiyoko Izawa Yuansong Bai Yasushi Soda Erika Sasaki Toshio Itoh Yoshiro Maru Satoshi Takahashi Kaoru Uchimaru Naoki Oyaizu Arinobu Tojo Chieko Kai Kenzaburo Tani 

作者机构:Central Institute for Experimental Animals Kawasaki Japan Department of Laboratory Medicine Research Hospital Institute of Medical Science the University of Tokyo Tokyo Japan Department of Molecular Genetics Medical Institute of Bioregulation Kyushu University Fukuoka Japan Department of Pharmacology Tokyo Woman’s Medical University Japan Division of Molecular Therapy Institute of Medical Science the University of Tokyo Tokyo Japan Laboratory Animal Research Center Institute of Medical Science the University of Tokyo Tokyo Japan. 

出 版 物:《Open Journal of Blood Diseases》 (血液病期刊(英文))

年 卷 期:2012年第2卷第1期

页      面:1-10页

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主  题:Leukemia Lentiviral Vector Myelofibrosis Common Marmoset 

摘      要:Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic *** this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.

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