The introduction of novel
immunomodulatory drugs (
IMiDs) has dramatically improved the survival of patients with
multiple myeloma (MM). While it has been shown that patients with specific cytogenetic subtypes, namely t(4;14), have the best outcomes when treated with
bortezomib-based regimens, the relationship between cytogenetic subtypes and response to
IMiDs remains unclear. Using
DNA synthesis assays, we investigated the relationship between cytogenetic subtype and
lenalidomide response in a representative panel of human myeloma cell lines (HMCLs). We examined HMCL
protein expression levels of the
lenalidomide target cereblon (CRBN) and its downstream target
interferon regulatory factor-4 (IRF4), which have previously been shown to be predictive of
lenalidomide response in HMCLs. Our results reveal that
lenalidomide response did not correlate with specific cytogenetic translocations. There were distinct groups of
lenalidomide-responsive and non-responsive HMCLs, as defined by inhibition of cellular proliferation; notably, all of the hyperdiploid HMCLs fell into the latter category. Repeated dosing of
lenalidomide significantly lowered the IC50 of the responsive HMCL ALMC-1 (IC50 = 2.6 μm vs. 0.005 μm, P < 0.0001), but did not have an effect on the IC50 of the non-responsive DP-6 HMCL (P > 0.05). Moreover, no association was found between
lenalidomide responsiveness and CRBN and IRF4 expression. Our data indicate that
lenalidomide sensitivity is independent of cytogenetic subtype in HMCLs. While CRBN and IRF4 have been shown to be associated with response to
lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment.