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Cancer Cell. 2015 May 11;27(5):671-81. doi: 10.1016/j.ccell.2015.04.004.

Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells.

Author information

1
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
2
Cancer Science Institute, National University of Singapore, Singapore 119077, Singapore.
3
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Institute of Biomedical Technologies, National Research Council (CNR), Pisa 56124, Italy.
4
Department of Specialized Medicine, University of Bologna, Bologna 40126, Italy.
5
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.

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.

PMID:
25965572
PMCID:
PMC4447336
DOI:
10.1016/j.ccell.2015.04.004
[Indexed for MEDLINE]
Free PMC Article

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