title: IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development.
abstract: 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.
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA. reynaudd@stemcell.ucsf.edu
authors.forename: Damien
authors.initials: D
authors.lastname: Reynaud
authors.forename: Eric
authors.initials: E
authors.lastname: Pietras
authors.forename: Keegan
authors.initials: K
authors.lastname: Barry-Holson
authors.forename: Alain
authors.initials: A
authors.lastname: Mir
authors.forename: Mikhail
authors.initials: M
authors.lastname: Binnewies
authors.forename: Marion
authors.initials: M
authors.lastname: Jeanne
authors.forename: Olga
authors.initials: O
authors.lastname: Sala-Torra
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Passegué
mesh_terms: D000818:Animals; D025461:Feedback, Physiological; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D039902:Multipotent Stem Cells / Q000473:pathology*; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism / Q000473:pathology
chemical_list: D015850:Interleukin-6; D016044:Fusion Proteins, bcr-abl
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