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

• 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; microenvironment; Microenvironments; Pathogenesis; Stromal cells; Survival; Targeted cancer therapy
• ISSN: 0278-0232; 1099-1069
• DOI: 10.1002/hon.2888

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.