Figure 1.

Anti-leukemia efficacy of cobimetinib and venetoclax in acute myeloid leukemia cell lines. Eleven acute myeloid leukemia cell lines were left untreated or treated with cobimetinib or venetoclax as single agents at 0.001, 0.01, 0.1, or 1.0 μM for 72 h. Calcusyn software was used to calculate the median inhibitory concentration (IC₅₀) values. Combinations of the two drugs were then tested on the same cell lines at dose ranges of 0.25, 0.5, 1, 2, and 4 times the IC₅₀ value of each compound. The combination index of each combination in each cell line was calculated on the basis on the luminescent intensity that correlated with number of viable cells determined by the CellTiter-Glo assay. Responses to treatment were categorized into four patterns: (i) sensitive to both drugs; (ii) sensitive only to cobimetinib and showing synergy for the combination; (iii) sensitive only to venetoclax and showing synergy for the combination; (iv) resistant to both drugs. AML: acute myeloid leukemia; Cobi: cobimetinib; Ven: venetoclax; CI: combination index