The Chemokine CCL3 Regulates Myeloid Differentiation and Hematopoietic Stem Cell Numbers
| Autor: | Alexandra N Goodman, Daniel K. Byun, Mary A. Georger, Rhonda J. Staversky, Michael W. Becker, Laura M. Calvi, Benjamin J. Frisch, Brandon J. Zaffuto |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myeloid Cellular differentiation lcsh:Medicine Cell Count Biology Article 03 medical and health sciences Mice immune system diseases hemic and lymphatic diseases parasitic diseases medicine Animals Myeloid Cells Progenitor cell lcsh:Science Chemokine CCL3 Mice Knockout Multidisciplinary lcsh:R Hematopoietic stem cell hemic and immune systems Cell Differentiation respiratory system medicine.disease Hematopoietic Stem Cells 3. Good health Haematopoiesis Leukemia 030104 developmental biology medicine.anatomical_structure Cancer research lcsh:Q Bone marrow Chronic myelogenous leukemia |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018) |
| ISSN: | 2045-2322 |
| Popis: | The chemokine CCL3 is frequently overexpressed in malignancies and overexpression leads to microenvironmental dysfunction. In murine models of chronic myelogenous leukemia (CML), CCL3 is critical for the maintenance of a leukemia stem cell population, and leukemia progression. With CCL3 implicated as a potentially viable therapeutic target, it is important to carefully characterize its role in normal hematopoietic homeostasis. CCL3−/− mice were used to evaluate the role of CCL3 in regulating hematopoietic stem and progenitor cell (HSPC) populations. CCL3−/− mice had loss of mature myeloid populations, while myeloid progenitors and HSPCs were increased, and microenvironmental populations were unchanged. These data show that CCL3 promotes myeloid lineage differentiation and the size of the HSPC pool independent of the supportive bone marrow microenvironment. Our results demonstrate a previously unrecognized role of CCL3 in the maintenance of homeostatic hematopoiesis that should be evaluated when targeting CCL3 signaling for the treatment of hematologic malignancy. |
| Databáze: | OpenAIRE |
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