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

Publication ,  Journal Article
Colmone, A; Amorim, M; Pontier, AL; Wang, S; Jablonski, E; Sipkins, DA
Published in: Science
December 19, 2008

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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Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 19, 2008

Volume

322

Issue

5909

Start / End Page

1861 / 1865

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Stem Cell Niche
  • Stem Cell Factor
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice
  • Leukemia, Myeloid, Acute
  • Humans
 

Citation

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Colmone, A., Amorim, M., Pontier, A. L., Wang, S., Jablonski, E., & Sipkins, D. A. (2008). Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science, 322(5909), 1861–1865. https://doi.org/10.1126/science.1164390
Colmone, Angela, Maria Amorim, Andrea L. Pontier, Sheng Wang, Elizabeth Jablonski, and Dorothy A. Sipkins. “Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.Science 322, no. 5909 (December 19, 2008): 1861–65. https://doi.org/10.1126/science.1164390.
Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008 Dec 19;322(5909):1861–5.
Colmone, Angela, et al. “Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.Science, vol. 322, no. 5909, Dec. 2008, pp. 1861–65. Pubmed, doi:10.1126/science.1164390.
Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008 Dec 19;322(5909):1861–1865.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 19, 2008

Volume

322

Issue

5909

Start / End Page

1861 / 1865

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Stem Cell Niche
  • Stem Cell Factor
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice
  • Leukemia, Myeloid, Acute
  • Humans