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. 2021 Oct;39(4):513-520.
doi: 10.1002/hon.2888. Epub 2021 May 20.

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

Csilla Kriston  1 , Márk Hernádfői  1 , Márk Plander  2 , Ágnes Márk  1 , Ferenc Takács  1 , Ágnes Czeti  1 , Gábor Szalóki  1 , Orsolya Szabó  1 , András Matolcsy  1 , Gábor Barna  1
Affiliations

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

Csilla Kriston et al. Hematol Oncol. 2021 Oct.

Abstract

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.

Keywords: CLL; IMIDs; bone marrow stromal cells; lenalidomide; microenvironment.

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References

REFERENCES

    1. Burger JA, Gribben JG. The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Seminars cancer Biol. 2014;24:71-81.
    1. Szurián K, Csala I, Marosvári D, et al. EZH2 is upregulated in the proliferation centers of CLL/SLL lymph nodes. Exp Mol pathology. 2018;105(2):161-165.
    1. Thijssen R, Slinger E, Weller K, et al. Resistance to ABT-199 induced by microenvironmental signals in chronic lymphocytic leukemia can be counteracted by CD20 antibodies or kinase inhibitors. Haematologica. 2015;100(8):e302-e306.
    1. Woyach JA, Furman RR, Liu T-M, et al. Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014;370(24):2286-2294.
    1. Fink AM, Bahlo J, Robrecht S, et al. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study. Lancet Haematol. 2017;4(10):e475-e486.

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