イワサキ　マサユキ   IWASAKI Masayuki   岩崎　正幸    所属   研究施設 研究施設    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model.
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：00064971/00064971
掲載区分	国外
巻・号・頁	105(2),pp.784-93
著者・共著者	Iwasaki Masayuki, Kuwata Takeshi, Yamazaki Yukari, Jenkins Nancy A, Copeland Neal G, Osato Motomi, Ito Yoshiaki, Kroon Evert, Sauvageau Guy, Nakamura Takuro
担当区分	筆頭著者
発行年月	2005/01
概要	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