Abstract
We investigated the procoagulant effects of lenalidomide (Len)-based regimens in vitro focusing on tissue factor (TF) and phosphatidylserine (PS). We examined the effects of a pharmacological concentration of Len with or without the corticosteroid dexamethasone (Dex) and the proteasome inhibitor bortezomib (Bor) using the human vascular endothelial cell line EAhy926 and the monocytic cell lines THP-1 and U937. Cell-surface procoagulant activity (PCA) was induced by Dex-containing regimens in all lines. Expression of TF antigen on the cell surface and of TF mRNA was markedly increased by Dex-containing regimens. PS exposure was increased modestly by a Len-based regimen. PS exposure was increased modestly in EAhy926 cells, and markedly increased in THP-1 and U937 cells by Bor-containing treatment. An anti-TF monoclonal antibody almost completely blocked the induced PCA. When Len is given in combination with Dex, PCA may be induced on endothelial cells and monocytes through TF expression and PS exposure.
Highlights
Multiple myeloma (MM) is characterized by the proliferation of clonal plasma cells in the bone marrow
Effects of Len, Dex, and Bor on cell surface procoagulant activity (PCA) We examined whether Len, Dex and Bor could increase cellsurface PCA in EAhy926, THP-1 and U937 cells (Fig. 1)
In THP-1 cells stimulated with Dex alone, PCA was induced significantly compared with control
Summary
Multiple myeloma (MM) is characterized by the proliferation of clonal plasma cells in the bone marrow. Several combinations of chemotherapy and/or autologous peripheral blood stem cell transplantation have been undertaken in MM patients. The new antineoplastic drugs thalidomide (Thal), lenalidomide (Len) and bortezomib (Bor) have been used to improve the response rates in the treatment of MM. Combination with corticosteroids enhances the tumoricidal effects [1,2,3,4]. Thal and Len were initially used for the treatment of relapsed/refractory MM, but both immunomodulatory drugs are being included in frontline regimens. Len has more potent antimyeloma properties than Thal and lacks many of its unfavorable features (including neurotoxicity). Len: has tumoricidal effects; interferes with the plasma cell– microenvironment interaction with subsequent downregulation of the crucial cytokines required for the growth of plasma cells; has immune stimulatory properties [2]
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