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      Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.

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          Abstract

          The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments that sequester transplanted human CD34+ (HPC-enriched) cells. CD34+ cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited CD34+ cell migration into malignant niches, normalized CD34+ cell numbers, and restored CD34+ cell mobilization in leukemic mice. These data suggest that the tumor microenvironment causes HPC dysfunction by usurping normal HPC niches and that therapeutic inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Dec 19 2008
          : 322
          : 5909
          Affiliations
          [1 ] Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue MC 2115, Chicago, IL 60637, USA.
          Article
          322/5909/1861
          10.1126/science.1164390
          19095944
          270e5e3b-25bf-4f03-b967-a2b233f933c7
          History

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