Fig. 5. Synergistic combinations of fadraciclib and venetoclax.

A Representative median-effect plots of the combination of fadraciclib and venetoclax in representative CLL samples cultured without BCA medium (#104) and with BCA medium (#54) and 2 samples with a high percentage of 17p deletion (#57, #77) cultured in BCA medium. B Comparison of the combination index for the combination of fadraciclib and venetoclax in CLL cells cultured without (gray column, 9 samples) or with BCA medium (white column, 7 samples). Data are presented as mean ± SE. C Representative immunoblotting of the combination of fadraciclib (Fad) and venetoclax (Ven) showing PARP cleavage and Mcl-1 and Bcl-2 protein levels. The CLL cells were incubated with 1 X IC₅₀ concentrations of each drug (measured previously for each sample) for 24 h. The percentage of cell viability relative to controls is shown below the images. D Time course of loss of CLL viability induced by fadraciclib, venetoclax, and the combination. CLL cells were incubated with the average IC₅₀ concentrations of fadraciclib (0.8 μM), venetoclax (0.07 μM), and the combination. Cell viability was measured at indicated times up to 24 h. Left: representative of 3 CLL samples without 17p deletion. Right: representative 2 CLL samples with 17p deletion (67% and 95% del17p). E Immunoblot showing the time effect of fadraciclib, venetoclax, and the combination in the samples described in D. F The levels of Mcl-1 (left) and Bcl-2 (right) were quantified in the blots and plotted as percentage of 0-h controls (mean ± SE of 3 samples).