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

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

.
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..

DOI: 10.4236/ojbd.2012.21001                

Abstract

Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In 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.

Keywords

Leukemia; Lentiviral Vector; Myelofibrosis; Common Marmoset

Conflicts of Interest

The authors declare no conflicts of interest.

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