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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: B-Lymphocytes, Cell Proliferation, Cell Survival, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Macrophages, Monocytes, Protein Kinase Inhibitors, Receptor Protein-Tyrosine Kinases, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Signal Transduction.
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Is colony-stimulating Factor-1 Receptor Required for Nurse-like Cell Survival in Chronic Lymphocytic Leukemia? Context: Monocytes and their progeny are abundant constituents of the tumor microenvironment in lymphoproliferative disorders, including chronic lymphocytic leukemia (CLL). Monocyte-derived cells, including nurse-like cells (NLC) in CLL, promote lymphocyte proliferation and survival, confer resistance to chemotherapy, and are associated with more rapid disease progression. Colony-stimulating factor-1 receptor (CSF-1R) regulates the homeostatic survival of tissue-resident macrophages. Therefore, we sought to determine whether CSF-1R is similarly required for NLC survival. CSF-1R expression by NLC was examined by flow cytometry and immunohistochemistry. CSF-1R blocking studies were performed using an antagonistic monoclonal antibody to examine its role in NLC generation and in CLL survival. A rational search strategy was performed to identify a novel tyrosine kinase inhibitor (TKI) targeting CSF-1R. The influence of TKI-mediated CSF-1R inhibition on NLC and CLL viability was examined. We demonstrated that the generation and survival of NLC in CLL is dependent upon CSF-1R signaling. CSF-1R blockade is associated with significant depletion of NLC and consequently inhibits CLL B-cell survival. We found that the JAK2/FLT3 inhibitor pacritinib suppresses CSF-1R signaling, thereby preventing the generation and survival of NLC and impairs CLL B-cell viability.
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CSF-1R is a novel therapeutic target that may be exploited in lymphoproliferative disorders, like CLL, that are dependent upon lymphoma-associated macrophages. Final Decision: yes