BCL-2 or MCL-1 inhibition synergizes with calcineurin blockade. (A) TMD8 xenograft mice were treated for 5 consecutive days with vehicle (n = 7) or 4 mg/kg FK506 (n = 6) and tumor volume was quantified by caliper measurements. FK506 significantly reduces tumor growth (P = .0093). (B) Average tumor weight of TMD8 xenograft mice after treatment of 9 days with vehicle (n = 7) or FK506 (n = 6). FK506 significantly reduces tumor mass (P = .0058). (C) TMD8 cells were transplanted in zebrafish embryos and tumor formation of treated animals was counted after 3 days by microscopy (n ≥ 20). (D) Representative images of transplanted zebrafish embryos after solvent or FK506 treatment. Arrow indicates the formation of a tumor. The ABC DLBCL cell lines HBL-1 or U2932 were treated with either (E) ABT-199 or (F) the MCL-1 inhibitor S63845 in the absence (left) or presence of CsA (right). Cell survival was quantified by an MTS assay. The combination index for CsA and ABT-199 in HBL-1 and U2932 is ≤0.17 and ≤0.34, respectively. For CsA and S68432, the combination index is ≤0.19 for HBL-1 and ≤0.23 for U2932. The data are representative of (E-F) at least 3 independent experiments. Error bars correspond to the mean ± SD. Statistical significance was calculated using Student t test (*P < .05, **P < .01, ***P < .001).