IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development

Cancer Cell. 2011 Nov 15;20(5):661-73. doi: 10.1016/j.ccr.2011.10.012.


Using a mouse model recapitulating the main features of human chronic myelogenous leukemia (CML), we uncover the hierarchy of leukemic stem and progenitor cells contributing to disease pathogenesis. We refine the characterization of CML leukemic stem cells (LSCs) to the most immature long-term hematopoietic stem cells (LT-HSCs) and identify some important molecular deregulations underlying their aberrant behavior. We find that CML multipotent progenitors (MPPs) exhibit an aberrant B-lymphoid potential but are redirected toward the myeloid lineage by the action of the proinflammatory cytokine IL-6. We show that BCR/ABL activity controls Il-6 expression thereby establishing a paracrine feedback loop that sustains CML development. These results describe how proinflammatory tumor environment affects leukemic progenitor cell fate and contributes to CML pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Feedback, Physiological
  • Fusion Proteins, bcr-abl / metabolism
  • Fusion Proteins, bcr-abl / physiology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-6 / physiology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Mice
  • Multipotent Stem Cells / pathology*
  • Precursor Cells, B-Lymphoid / metabolism
  • Precursor Cells, B-Lymphoid / pathology


  • Interleukin-6
  • Fusion Proteins, bcr-abl