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

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Interleukin-2
Stem cells
Leukemia
Purification
Cytokines
Stem Cell Niche
Myeloid Cells
Mast Cells
Cell Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kobayashi, C. I., Takubo, K., Kobayashi, H., Nakamura-Ishizu, A., Honda, H., Kataoka, K., ... 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

The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. / Kobayashi, Chiharu I.; Takubo, Keiyo; Kobayashi, Hiroshi; Nakamura-Ishizu, Ayako; Honda, Hiroaki; Kataoka, Keisuke; Kumano, Keiki; Akiyama, Hideo; Sudo, Tetsuo; Kurokawa, Mineo; Suda, Toshio.

In: Blood, Vol. 123, No. 16, 17.04.2014, p. 2540-2549.

Research output: Contribution to journalArticle

Kobayashi, CI, 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, vol. 123, no. 16, pp. 2540-2549. https://doi.org/10.1182/blood-2013-07-517847
Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K et al. The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. Blood. 2014 Apr 17;123(16):2540-2549. https://doi.org/10.1182/blood-2013-07-517847
Kobayashi, Chiharu I. ; Takubo, Keiyo ; Kobayashi, Hiroshi ; Nakamura-Ishizu, Ayako ; Honda, Hiroaki ; Kataoka, Keisuke ; Kumano, Keiki ; Akiyama, Hideo ; Sudo, Tetsuo ; Kurokawa, Mineo ; Suda, Toshio. / The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. In: Blood. 2014 ; Vol. 123, No. 16. pp. 2540-2549.
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