BCL6 is required for a basic level of Imatinib-resistance in CML cells. (A) BCL6^−/− and BCL6^+/+ CML-like cells were treated with Imatinib at various concentrations for 3 d, and cell metabolism was measured in a Resazurin assay. Mean values ± SD of three experiments are depicted. (B) BCL6^+/+ and BCL6^−/− CML cells were treated with Imatinib as in A, and apoptosis was assessed by flow cytometry analysis of 7AAD and annexin V. Mean values ± SD of three experiments are depicted. (C) BCL6^−/− CML-like cells were transduced with 4-OHT–inducible BCL6 (BCL6-ER^T2/GFP) or an ER^T2/GFP empty vector control. BCL6^−/− CML-like cells were then treated with 1 μmol/liter Imatinib for the times indicated and in the presence of 4-OHT–mediated induction of BCL6-ER^T2 or ER^T2. Percentage of GFP⁺ cells were measured by flow cytometry as an indication of a BCL6-ER^T2– or ER^T2-mediated survival advantage. A time course of mean values ± SD of three experiments is depicted in C, and examples of the flow cytometry plots are shown in D. (E) Human CML cell lines (KCL22, JURL, LAMA84, KYO1, and KU812) were incubated in the presence or absence of 1 µmol/liter Imatinib, 5 µmol/liter RI-BPI, or a combination of both for 3 d. Viability was measured by flow cytometry. Mean values, SD, and p-values from three experiments are indicated.