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Leukemic Cells Create Bone Marrow Niches That Disrupt the Behavior of Normal Hematopoietic Progenitor Cells
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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“Consequently, LSCs are able to escape the cytotoxic effects of chemotherapy and give rise to the relapse of the disease, which occurs in a large majority of acute myeloid leukemia (AML) patients [12,13].”
From Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2 (2015) · cites this paper as [12]
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Giustacchini, A., Thongjuea, S., Barkas, N., Woll, P. S., Povinelli, B. J., Booth, C. A. G., Sopp, P., Norfo, R., Rodriguez-Meira, A., Ashley, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4336 · Cited by 403
Hanoun, M., Zhang, D., Mizoguchi, T., Pinho, S., Pierce, H., Kunisaki, Y., Lacombe, J., Armstrong, S. A., Dührsen, U., & Frenette, P. S. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.06.020 · Cited by 381
Epidemiology, Staging, and Management of Multiple Myeloma
Padala, S. A., Barsouk, A., Barsouk, A., Rawla, P., Vakiti, A., Kolhe, R., Kota, V., & Ajebo, G. H. (2021) · Medical Sciences · doi:10.3390/medsci9010003 · Cited by 332
“The accumulation of the monoclonal antibody, Bence–Jones proteins, can precipitate in the urine resulting in kidney damage (usually type 2 renal tubular acidosis) and renal failure, and it can be seen in two-thirds of MM cases [2].”
BackgroundInfluentialMechanisms of tumor cell extravasation in an in vitro microvascular network platform
Chen, M. B., Whisler, J. A., Jeon, J. S., & Kamm, R. D. (2013) · Integrative Biology · doi:10.1039/c3ib40149a · Cited by 308
Metadata
- Authors
- Colmone, A., Amorim, M., Pontier, A. L., Wang, S., Jablonski, E., & Sipkins, D. A.
- Affiliations
- Department of Medicine, Section of Hematology/Oncology, The University of Chicago, 5841 South Maryland Avenue MC 2115, Chicago, IL 60637, USA.
- Venue
- Science
- Published
- 2008-12-19
- Volume
- 322
- Issue
- 5909
- Pages
- 1861-1865
- ISSN
- 0036-8075
- 1095-9203
- Cited by
- 541
- References
- 0
- Language
- en
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- The paper
- 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. https://doi.org/10.1126/science.1164390
