Figure 4.

Synergy between voreloxin and Ara-C was investigated in 25 primary AML samples over 48 h in vitro. The ratio between voreloxin and Ara-C was kept constant at 2:1 at all times. This ratio was determined experimentally based on the relative sensitivity of primary samples to voreloxin and Ara-C. (A) Dose response curves to voreloxin, Ara-C and both drugs combined in a representative primary AML sample illustrating the different responses to voreloxin, Ara-C and both drugs in combination (B) Fractional effect plot where synergy (identified by a combination index <1) is demonstrated over a range of drug concentrations. (C) Combination index plot. The combination index at the LD₅₀ of all 25 primary samples tested is shown. Synergy between the two agents was found in 22 of the 25 samples. The samples in which synergy was not shown were particularly sensitive to one of the agents when tested separately. The mean combination index was 0.798. (D) The combination index (CI) values for the combinations of voreloxin plus Ara-C and of Ara-C plus etoposide are shown for NB4 and HL-60 cells. The combination of Ara-C and either voreloxin or etoposide showed synergy in NB4 cells while in HL-60 cells there was an additive response when voreloxin and Ara-C were combined and antagonism when Ara-C and etoposide were used in combination.