Abstract
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of small, mature CD5+ B lympho-cytes in the blood, marrow, and lymphoid organs. Cell survival depends on interaction with the leukemic microenvironment. However, the mechanisms controlling CLL cell survival are still incompletely understood. Macrophage migration-inhibitory factor (MIF), a pro-inflammatory and immunoregulatory chemokine-like cytokine, interacts with CXCR4, a major chemokine receptor, as well as with CD74/invariant chain, a single -pass type II receptor. In this study, we analyzed the roles of CXCR4, CD74, and MIF in CLL. Mononuclear cells from patients with hematological malignancies were analyzed for coexpression of CXCR4 and CD74 by flow cytometry. Strong co-and overexpression of CXCR4 and CD74 were observed on B cells of CLL patients (n = 10). Survival and chemotaxis assays indicated that CXCR4 and CD74 work together to enhance the survival and migration of malignant cells in CLL. Blockade of the receptors, either individually or in com-bination, promoted cell death and led to an abrogation of MIF-driven migration responses in murine and human CLL cells, suggesting that joint activation of both receptors is crucial for CLL cell survival and mobility. These findings indicate that the MIF/CXCR4/CD74 axis represents a novel therapeutic target in CLL. (c) 2022 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin
Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 0301-472X |
| Sprache: | Englisch |
| Dokumenten ID: | 112152 |
| Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2024, 07:33 |
| Letzte Änderungen: | 06. Jun. 2024, 16:37 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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