Figure 1.

Chemical segregation of navitoclax activity in NHL cell lines; requirement for BCL-2 or BCL-X_L for survival. The efficacy of navitoclax, venetoclax or A-1155463 was determined in NHL cell lines as described in the Materials and Methods section. EC₅₀s were calculated from the resulting sigmoidal dose/response curves (see Supplementary Table 1) and segregated according to their BCL2^High or BCL2^Low status.²⁰ Data are presented as the mean of at least three independent experiments. Cell lines with navitoclax EC₅₀s >2 μM were deemed resistant. Data are presented as the mean of at least three independent experiments (a). Expression of anti-apoptotic BCL-2 family proteins was determined by Luminex as described and segregated according to the BCL2^High or BCL2^Low status. The median is shown in red and the Mann–Whitney U-test was used to determine statistical significance. NS, not significant (b). Navitoclax-resistant BCL2^High cells were treated with navitoclax or venetoclax (both 1 μM) for 8 h and the interaction of BIM with BCL-2 or MCL-1 assessed using an Electrochemiluminescent ELISA (MSD) as described in the Materials and Methods section. Data are presented as the mean±s.e.m. of three independent experiments (c).