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M. B. Bradley, P. Satwani, L. Baldinger, E. Morris, C. van de Ven, G. Del Toro, J. Garvin, D. George, M. Bhatia, E. Roman, L. A. Baxter-Lowe, J. Schwartz, E. Qualter, R. Hawks, K. Wolownik, S. Foley, O. Militano, J. Leclere, Y. K. Cheung and M. S. Cairo, “Reduced Intensity Allogeneic Umbilical Cord Blood Transplantation in Children and Adolescent Recipients with Malignant and Non-Malignant Diseases,” Bone Marrow Transplant, Vol. 40, No. 7, 2007, pp. 621-631. doi:10.1038/sj.bmt.1705785

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

  AUTHORS: 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

  KEYWORDS: Leukemia; Lentiviral Vector; Myelofibrosis; Common Marmoset

  JOURNAL NAME: Open Journal of Blood Diseases, Vol.2 No.1, March 1, 2012

  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.