title: Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells.
abstract: Leukemic cells disrupt normal patterns of blood cell formation, but little is understood about the mechanism. We investigated whether leukemic cells alter functions of normal hematopoietic stem and progenitor cells. Exposure to chronic myelogenous leukemia (CML) caused normal mouse hematopoietic progenitor cells to divide more readily, altered their differentiation, and reduced their reconstitution and self-renewal potential. Interestingly, the normal bystander cells acquired gene expression patterns resembling their malignant counterparts. Therefore, much of the leukemia signature is mediated by extrinsic factors. Indeed, IL-6 was responsible for most of these changes. Compatible results were obtained when human CML were cultured with normal human hematopoietic progenitor cells. Furthermore, neutralization of IL-6 prevented these changes and treated the disease.
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Welner
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 119077, Singapore.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bararia
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Akos
authors.initials: A
authors.lastname: Czibere
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 119077, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lorena Lobo De Figueiredo
authors.initials: LL
authors.lastname: Pontes
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Institute of Biomedical Technologies, National Research Council (CNR), Pisa 56124, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Ruscio
authors.affiliation: Department of Specialized Medicine, University of Bologna, Bologna 40126, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Cancer Science Institute, National University of Singapore, Singapore 119077, Singapore. Electronic address: daniel.tenen@nus.edu.sg.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D051379:Mice; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D015850:Interleukin-6