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

Blood. 2014 Apr 17;123(16):2540-9. doi: 10.1182/blood-2013-07-517847. Epub 2014 Feb 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation, Leukemic
  • Humans
  • Interleukin-2 / physiology*
  • Interleukin-2 Receptor alpha Subunit / physiology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / physiology*
  • Signal Transduction / physiology
  • Th2 Cells / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology


  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit