The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells

Chiharu I. Kobayashi, Keiyo Takubo, Hiroshi Kobayashi, Ayako Nakamura-Ishizu, Hiroaki Honda, Keisuke Kataoka, Keiki Kumano, Hideo Akiyama, Tetsuo Sudo, Mineo Kurokawa, Toshio Suda

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 CD251F2LSK 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.

Original languageEnglish
Pages (from-to)2540-2549
Number of pages10
JournalBlood
Volume123
Issue number16
DOIs
Publication statusPublished - 2014 Apr 17
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kobayashi, C. I., Takubo, K., Kobayashi, H., Nakamura-Ishizu, A., Honda, H., Kataoka, K., Kumano, K., Akiyama, H., Sudo, T., Kurokawa, M., & Suda, T. (2014). The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. Blood, 123(16), 2540-2549. https://doi.org/10.1182/blood-2013-07-517847