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	Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential.
掲載誌名	正式名：Genes & development 略　 称：Genes Dev ISSNコード：08909369/08909369
掲載区分	国外
巻・号・頁	21(21),pp.2762-74
著者・共著者	Wong Piu, Iwasaki Masayuki, Somervaille Tim C P, So Chi Wai Eric, So Chai Wai Eric, Cleary Michael L
担当区分	2nd著者
発行年月	2007/11
概要	Oncogenic mutations of the MLL histone methyltransferase confer an unusual ability to transform non-self-renewing myeloid progenitors into leukemia stem cells (LSCs) by mechanisms that remain poorly defined. Misregulation of Hox genes is likely to be critical for LSC induction and maintenance but alone it does not recapitulate the phenotype and biology of MLL leukemias, which are clinically heterogeneous--presumably reflecting differences in LSC biology and/or frequency. TALE (three-amino-acid loop extension) class homeodomain proteins of the Pbx and Meis families are also misexpressed in this context, and we thus employed knockout, knockdown, and dominant-negative genetic techniques to investigate the requirements and contributions of these factors in MLL oncoprotein-induced acute myeloid leukemia. Our studies show that induction and maintenance of MLL transformation requires Meis1 and is codependent on the redundant contributions of Pbx2 and Pbx3. Meis1 in particular serves a major role in establishing LSC potential, and determines LSC frequency by quantitatively regulating the extent of self-renewal, differentiation arrest, and cycling, as well as the rate of in vivo LSC generation from myeloid progenitors. Thus, TALE proteins are critical downstream effectors within an essential homeoprotein network that serves a rate-limiting regulatory role in MLL leukemogenesis.
DOI	10.1101/gad.1602107
PMID	17942707