IWASAKI Masayuki
Department Research Institutes and Facilities, Research Institutes and Facilities Position Assistant Professor |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. |
Journal | Formal name:Blood Abbreviation:Blood ISSN code:00064971/00064971 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 105(2),pp.784-93 |
Author and coauthor | Iwasaki Masayuki, Kuwata Takeshi, Yamazaki Yukari, Jenkins Nancy A, Copeland Neal G, Osato Motomi, Ito Yoshiaki, Kroon Evert, Sauvageau Guy, Nakamura Takuro |
Authorship | Lead author |
Publication date | 2005/01 |
Summary | The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis. |
DOI | 10.1182/blood-2004-04-1508 |
PMID | 15454493 |