イシズ　アヤコ   Ayako Nakamura-Ishizu   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells.
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：15280020/00064971
掲載区分	国外
巻・号・頁	123(16),pp.2540-9
著者・共著者	Kobayashi Chiharu I, Takubo Keiyo, Kobayashi Hiroshi, Nakamura-Ishizu Ayako, Honda Hiroaki, Kataoka Keisuke, Kumano Keiki, Akiyama Hideo, Sudo Tetsuo, Kurokawa Mineo, Suda Toshio
発行年月	2014/04
概要	Just as normal stem cells require niche cells for survival, leukemia-initiating cells (LICs) may also require niche cells for their maintenance. Chronic myeloid leukemia (CML) is caused by the activity of BCR-ABL, a constitutively active tyrosine kinase. CML therapy with tyrosine kinase inhibitors is highly effective; however, due to the persistence of residual LICs, it is not curative. Several factors are known to support CML LICs, but purification of LICs and a thorough understanding of their niche signals have not yet been achieved. Using a CML-like mouse model of myeloproliferative disease, we demonstrate that CML LICs can be divided into CD25(+)FcεRIα(-) Lineage marker (Lin)(-) Sca-1(+)c-Kit(+) (F(-)LSK) cells and CD25(-)F(-)LSK cells. The CD25(+)F(-)LSK cells had multilineage differentiation capacity, with a preference toward cytokine-producing mast cell commitment. Although cells interconverted between CD25(-)F(-)LSK and CD25(+)F(-)LSK status, the CD25(+)F(-)LSK cells exhibited higher LIC capacity. Our findings suggest that interleukin-2 derived from the microenvironment and CD25 expressed on CML LICs constitute a novel signaling axis. The high levels of CD25 expression in the CD34(+)CD38(-) fraction of human CML cells indicate that CD25(+) LICs constitute an "LIC-derived niche" that could be preferentially targeted in therapy for CML.
DOI	10.1182/blood-2013-07-517847
PMID	24574458