Fig. 3

FBXW7 mutations caused resistance to c-MYC inhibitors. JQ1 (c-MYC inhibitor) (a), OTX-015 (c-MYC inhibitor) (b) and AG-490 (JAK2 inhibitor) (c) reduced HTLV-I/ATL-lines proliferation in a dose-dependent manner. Cells were treated with the indicated concentration of inhibitor or dimethyl sulfoxide (DMSO) for 72 h. Each cell line was treated at least twice for standard deviation. Cell proliferation was analyzed by XTT assay (Roche). Overexpression of FBXW7 WT in MT1 didn’t affect JQ1 (a), OTX-015 (b) and AG-490 (c) sensitivity. Western blot analysis showed the reduced expression of c-MYC by JQ1 and OTX-015. Expression of FBXW7 mutants caused resistance to JQ1 (a) and OXT-015 (b) treatment, but not AG-490 (c) treatment. MT1 cells expressing the indicated FBXW7 wild-type or FBXXW7 mutants were treated with JQ1/OTX-015/AG-490 or dimethyl sulfoxide (DMSO). Cell proliferation was analyzed by XTT assay (Roche). Dinaciclib (cyclin E inhibitor) (d) and Sorafenib (MCL1 inhibitor) (e) reduced HTLV-I/ATL-lines proliferation in a dose-dependent manner. Cells were treated with the indicated concentration of inhibitor or dimethyl sulfoxide (DMSO) for 72 h. Each cell line was treated at least twice for standard deviation. Cell proliferation was analyzed by XTT assay (Roche). Expression of FBXW7 mutants caused resistance to Dinaciclib (cyclin E inhibitor) (a) and Sorafenib (MCL1 inhibitor) (b) treatment. MT1 cells expressing indicated FBXW7 wild-type or FBXW7 mutants were treated with Dinaciclib/Sorafenib or dimethyl sulfoxide (DMSO) for 72 h. Cell proliferation was analyzed by XTT assay (Roche)