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

• 作者: Arinobu Tojo Chieko Kai Erika Sasaki Kaoru Uchimaru Kenzaburo Tani Kiyoko Izawa Manabu Ozawa Naoki Oyaizu Satoshi Takahashi Seiichiro Kobayashi Takafumi Hiramoto Toshio Itoh Yamin Tian Yan Dong Yasushi Soda Yoshiro Maru Yuansong Bai
• 来源期刊: 血液病期刊(英文)
• 学科: 医学
• 关键词: LEUKEMIA LENTIVIRAL Vector MYELOFIBROSIS Common MARMOSET
• 年，卷（期）: 2012,（1）
• 页码范围: 1-10
• 页数: 10页
• 分类号: R73

摘要

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.