Correlation Of Tumoricidal Activity Of Lenalidomide Against Hematologic Tumor Cells With Cyclin D1/D2 Expression And Effect On Tumor-Suppressor Gene Upregulation.

8090 Background: Lenalidomide (len) treatment leads to cell cycle arrest and apoptosis in some but not all multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) cell lines. Len treatment of sensitive cells appears to up-regulate tumor suppressor gene expression. We sought to define the role of baseline and len-induced expression of cyclin D family members and tumor suppressor genes in mantle cell lymphoma (MCL) and MM cell lines with the aim of identifying correlates to len-induced anti-proliferative activity. Methods: Anti-proliferative activity was assessed in a panel of 10 MM and 14 NHL cell lines as well primary cells derived from 3 MM and 2 MCL patients. Anti-proliferative activity (at 72 hrs) was correlated with baseline and len-induced expression of cyclins D1-3 and multiple tumor suppressor genes measured by RT-PCR. The effect of len on the nuclear localization of p27 protein was also assessed. Results: In MM and MCL cells sensitivity to len-mediated anti-proliferative activity appeared to correlate with baseline expression of cyclin D1 (p