Six of 9 MCL cell lines show synergistic killing with treatment with PRT382 and BCL-2 inhibition, venetoclax. (A) IC50 of 9 MCL cell lines measured with annexin V/PI and flow cytometry after 72 hours of treatment with venetoclax. Cell lines with an IC50 below 1 μM are starred and considered sensitive. (B) Synergy matrices calculated through Combenefit54 using the Lowe model of synergy. Values below −10 are antagonistic, −10 to 10 are additive, and values over 10 are synergistic. Significance is shown by stars at the bottom of each box. ∗P < .05; ∗∗P < .01; ∗∗∗ P < .001. (C) Single synergy values calculated from at least 3 separate replicates for each cell line. The same levels of synergy are used as with the synergy matrices. (D) Western blot showing the baseline levels of key proteins in MCL cell lines and normal donor B Cells (ND B cells) without and with IgG stimulation. Values are corrected by the loading control and normalized to Jeko. (E) The correlation between the baseline level of BCL-2 protein and the Lowe score seen across the MCL cell lines (Maver-1 was censored as an outlier). (F) Correlation between P53 status and synergy score. (G) Western blot showing the baseline levels of key proteins in Jeko, 5 primary patient peripheral blood mononuclear cells (PBMCS), and 2 PDX murine models of MCL. Values are corrected by the loading control and normalized to Jeko. A Spearman correlation (E) or Student t test (F) was used to determine significance P < .05; ∗∗P < .01 ∗∗∗P < .001.
