Suppression of CRBN confers lenalidomide resistance. Three myeloma cell lines were infected with NT and CRBN shRNA-expressing lentivirus. Most CRBN shRNA-expressing myeloma cells died within the first week after infection. An average of 30% of myeloma cells survived, and those cells plus NT control expressing cells were sorted for GFP expression at 3 weeks after infection (A). CRBN expression level in each pair of sorted NT and CRBN shRNA-expressing cells was measured by quantitative PCR (B). (C) Activity of lenalidomide on sorted myeloma cell lines was measured by MTT assay.