The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
CXCR4 Regulates Migration and Development of Human Acute Myelogenous Leukemia Stem Cells in Transplanted NOD/SCID Mice
Open accessAbstract
The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 participate in the retention of normal hematopoietic stem cells within the bone marrow (BM) and their release into the circulation. Homing and engraftment of human stem cells in immunodeficient mice are dependent on cell surface CXCR4 expression and the production of BM SDF-1, which acts also as a survival factor for both human and murine stem cells. However, the role of SDF-1/CXCR4 interactions in the control of human acute myelogenous leukemia (AML) cell trafficking and disease progression is poorly understood. In this study, we report that although some AML cells do not express surface CXCR4, all AML cells tested express internal CXCR4 and SDF-1. Culture of AML cells with SDF-1 promoted their survival, whereas addition of neutralizing CXCR4 antibodies, SDF-1 antibodies, or AMD3100 significantly decreased it. Pretreatment of primary human AML cells with neutralizing CXCR4 antibodies blocked their homing into the BM and spleen of transplanted NOD/SCID/B2mnull mice. Furthermore, weekly administrations of antihuman CXCR4 to mice previously engrafted with primary AML cells led to a dramatic decrease in the levels of human AML cells in the BM, blood, and spleen in a dose- and time-dependent manner. Interestingly, the same treatment did not affect significantly the levels of normal human progenitors engrafted into NOD/SCID mice. Taken together, our findings demonstrated the importance of the SDF-1/CXCR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.
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Cites
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Self-citationFunction of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development
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Cited by
Stem cell concepts renew cancer research
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How do stem cells find their way home?
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CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers
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Metadata
- Authors
- Tavor, S., Petit, I., Porozov, S., Avigdor, A., Dar, A., Leider-Trejo, L., Shemtov, N., Deutsch, V., Naparstek, E., Nagler, A., & Lapidot, T.
- Venue
- Cancer Research
- Published
- 2004-04-15
- Volume
- 64
- Issue
- 8
- Pages
- 2817-2824
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2162995424
- Cited by
- 363
- References
- 50
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: CXCR4 Regulates Migration and Development of Human Acute Myelogenous Leukemia Stem Cells in Transplanted NOD/SCID Mice. https://app.cochat.ai/papers/10.1158/0008-5472.can-03-3693
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- Tavor, S., Petit, I., Porozov, S., Avigdor, A., Dar, A., Leider-Trejo, L., Shemtov, N., Deutsch, V., Naparstek, E., Nagler, A., & Lapidot, T. (2004). CXCR4 Regulates Migration and Development of Human Acute Myelogenous Leukemia Stem Cells in Transplanted NOD/SCID Mice. Cancer Research. https://doi.org/10.1158/0008-5472.can-03-3693
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