Ayako Nakamura-Ishizu
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells.
Journal Formal name:Blood
ISSN code:15280020/00064971
Domestic / ForeginForegin
Volume, Issue, Page 123(16),pp.2540-9
Author and coauthor Kobayashi Chiharu I, Takubo Keiyo, Kobayashi Hiroshi, Nakamura-Ishizu Ayako, Honda Hiroaki, Kataoka Keisuke, Kumano Keiki, Akiyama Hideo, Sudo Tetsuo, Kurokawa Mineo, Suda Toshio
Publication date 2014/04
Summary 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