The most stringent definition of therapeutic synergy is just a therapeutic effect achieved with a tolerated regimen of a combination therapy that exceeds the effect achieved at any tolerated dose of monotherapy associated with the same drugs utilized in the combination. These results provide additional evidence for the rational combination of the Bcl Dovitinib structure 2 inhibitor with L asp or TPT in the treatment of pediatric ALL. Fixed ratio mix cytotoxicity assays were completed on yet another five xenografts, to check the generality of our results, and all showed synergy or strong synergy between ABT 737 and T asp or TPT. Rationale for Combining ABT 737, TPT, and M asp in the Treatment of ALL. Since we’ve demonstrated above that ABT 737 puts synergistic ex vivo and in vivo antileukemic results when coupled with either TPT or L asp, we further explored the explanation to develop this three drug combination. First, we examined the results of these drugs on the levels of important apoptosis regulatory proteins in ex vivo cultured Cellular differentiation xenograft cells. Consistent with its qualities like a DNAdamaging agent, a focus of TPT that’s possible in the plasma of patients with cancer caused a transient increase in p53 expression in MOST 19 cells within 2 h of exposure but had no major effects on the levels of the antiapoptotic proteins Mcl 1, Bcl 2, Bcl w, or Bcl XL or pro apoptotic Noxa, Puma, or Bim. In comparison, exposure of ALL 19 cells to L asp caused a rapid and specific down regulation of Mcl 1 compared with other Bcl 2 family proteins and only a delayed induction of p53. This effect was established in two additional xenografts after having a 4 h exposure to either L asp or TPT. These results claim that L asp, TPT, and ABT 737 target nonoverlapping the different parts of the intrinsic apoptosis pathway, which might end in cytotoxicity against ALL cells ex vivo and in vivo. With this assumption, we tested the triple drug combination against met inhibitors ALL 19. The combination of L asp, TPT, and ABT 737 was strongly synergistic ex vivo, while the combination of TPT with L asp was reasonably hostile. It’s significant that the three drug combination delayed the in vivo development of MOST 19 by 50 times longer than expected if the effects of the three drugs were simply additive. In this experiment, L asp and ABT 737 alone were ineffective in delaying the progression of ALL 19, TPT caused a substantial delay, whereas the triple combination triggered a delay of 85. 5 days. In the triple combination class, only three of seven mice reached a leukemia related function, deaths of the rest of the mice were assumed to be age related. It is significant the in vivo synergistic effect of the double combination was much greater than either the combination of ABT 737/L asp or ABT 737/TPT. To confirm the generality of the in vivo synergy between TPT, M asp, and ABT 737 an additional two chemoresistant xenografts were tested.