Combined targeting of MYC and BCL6 severely impairs BL growth in mice by reducing proliferation and increasing apoptosis. (A) Growth of tumor xenografts of RAJI cells transduced with doxycycline-inducible Omomyc vector in NSG mice. Lymphoma cells were treated with BI-3802 (5 μM) for 24 hours before injection. Mice were administered normal water (red line) or doxycycline water (blue line) from day 0. Data are mean ± standard error of the mean of 8 tumors per group. *P < .05, paired 2-tailed Student t test. (B) Representative H&E stains (top row) and immunohistochemistry for cleaved caspase 3 (middle row) and Ki-67 (bottom row) performed on RAJI lymphoma arising in NSG mice and treated with the BCL6 degrader BI-3802 together with Omomyc, as in (A) (original magnification ×200). Scale bars, 50 μm. Quantification of cleaved caspase 3⁺ (C) and Ki-67⁺ (D) cells in RAJI lymphoma with the indicated treatment. Data were obtained from 4 areas in 4 independent tumors for each treatment. Data are mean ± standard deviation. **P < .01, unpaired 2-tailed Student t test. (E) Representative immunofluorescence performed on RAJI lymphoma grafted in NSG mice and treated with the BCL6 degrader BI-3802 together with Omomyc, as in (A). Cells were stained for Ki-67 (green), Omomyc (red), and DAPI (blue) for the nucleus (original magnification, ×200). Scale bars, 100 μm. Higher-magnification images of the white boxes are shown in the far right panels. Pink arrow-heads in inset images indicate Ki-67⁻/Omomyc⁺ nuclei. (F) Quantification of the experiment described in (E). Three sections for each treatment were used to score the number of Ki-67⁺/Omomyc⁻ and Ki-67⁺/Omomyc⁺ nuclei. ***P < .001.