Lenalidomide abrogates the survival effect of bone marrow stromal cells in chronic lymphocytic leukemia

In the pathogenesis of chronic lymphocytic leukemia (CLL) the microenvironment plays an important role, as it produces survival signals and mediates drug resistance. Lenalidomide, which has immunomodulatory effect, can enhance the activation of T‐, NK‐cells and endothelial cells, however there are n...

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Bibliographic Details
Published in:Hematological oncology 2021-10, Vol.39 (4), p.513-520
Main Authors: Kriston, Csilla, Hernádfői, Márk, Plander, Márk, Márk, Ágnes, Takács, Ferenc, Czeti, Ágnes, Szalóki, Gábor, Szabó, Orsolya, Matolcsy, András, Barna, Gábor
Format: Article
Language:English
Subjects:
Agent Orange
Antigens
Apoptosis
Bone marrow
bone marrow stromal cells
CD49d antigen
CD86 antigen
Cell activation
Chronic lymphocytic leukemia
CLL
Cytokines
Drug resistance
Endothelial cells
Flow cytometry
IMIDs
Immunogenicity
Immunomodulation
Immunotherapy
Interferon regulatory factor 4
lenalidomide
Leukemia
Lymphatic leukemia
Medicin och hälsovetenskap
microenvironment
Microenvironments
Pathogenesis
Stromal cells
Survival
Targeted cancer therapy
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Summary:In the pathogenesis of chronic lymphocytic leukemia (CLL) the microenvironment plays an important role, as it produces survival signals and mediates drug resistance. Lenalidomide, which has immunomodulatory effect, can enhance the activation of T‐, NK‐cells and endothelial cells, however there are no data available whether it can modulate bone marrow stromal cells (BMSCs). In our study, we investigated the effects of lenalidomide on BMSCs and CLL cells. CLL cells were cultured alone or with BMSCs and were treated with lenalidomide. Apoptosis, immunophenotype, and cytokine secretion of BMSCs and CLL cells were determined by flow cytometry. Lenalidomide slightly increased the apoptosis of CLL cells and abrogated the anti‐apoptotic effect of BMSCs on CLL cells. Lenalidomide treatment decreased the expression of antigens on CLL cells, which mediate the interactions with the microenvironment. Interestingly, lenalidomide enhanced the expression of IRF4 and the co‐stimulatory molecule CD86. The secretion of several cytokines was not changed significantly by lenalidomide. CD49d‐negative CLL cases were more sensitive to lenalidomide treatment. Our results suggest that lenalidomide has a limited effect on BMSCs, but it renders CLL cells more immunogenic and unresponsive to survival signals provided by BMSCs.
ISSN:0278-0232
1099-1069
1099-1069
DOI:10.1002/hon.2888