Cyclosporine Broadens the Therapeutic Potential of Lenalidomide in Myeloid Malignancies

/calpain pro-apoptotic pathway, while upregulation of RCAN1 inhibited the CaN pro-survival pathway in MDSL cells. Notably, the pharmacological CaN inhibitor, cyclosporine, enhanced the sensitivity to lenalidomide in MDS as well as acute myeloid leukemia (AML). Surprisingly, pretreatment with lenalidomide reversed the immunosuppressive effects of cyclosporine on T lymphocytes. Our studies suggest that lenalidomide mediates degradation of IKZF1, leading to derepression of GPR68 and RCAN1 that activates the Ca2+/calpain pro- apoptotic pathway and inhibits the CaN pro-survival pathway, respectively. Our studies implicate that cyclosporine extends the therapeutic potential of lenalidomide to myeloid malignancies without compromising immune function.