GCK inhibition overcomes LEN resistance in MM cells. (A) MM.1S and MM.1S-LEN^RES were treated with LEN at the indicated concentrations for 24 hours. CRBN, IKZF1, c-MYC, IKZF3, and IRF4 protein levels in cell lysates were examined by western blotting. (B) MM.1S and MM.1S-LEN^RES were treated with LEN at the indicated concentrations for 3 days for cell proliferation detected by AQueous One Solution Cell Proliferation Assay (MTS). (C) MM.1S and MM.1S-LEN^RES were cultured in the presence of TL4-12 at the indicated concentrations for 24 hours to analyze CRBN, IKZF1, c-MYC, IKZF3, and IRF4 expression by western blotting. (D) MM.1S and MM.1S-LEN^RES were treated with TL4-12 at the indicated concentrations for 3 days for cell proliferation detected as in panel B. IC50, 50% inhibitory concentration.