Figure 6 | Leukemia

Figure 6

From: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

Figure 6

Inhibiting JAK in combination with the MAPK, PI3K and Bcl-2 pathway results in synergistic or additive effects on Ba/F3 cells transformed by JAK3 mutants. (a) Chou-Talalay plots showing the effect of tofacitinib with MEK inhibitors (selumetinib, trametinib), Bcl-2 inhibitor (ABT-199) or PI3K inhibitor (buparlisib) on Ba/F3 cells transformed by JAK3 M511I or L857Q after 24 h incubation. CompuSyn was used to calculate the combination index (CI). CI<1 indicate synergistic effects, C=1 indicate additive effects, C>1 indicate antagonistic effects. (b) Ba/F3 transformed by M511I or L857Q were treated for 24 h with single compounds or combination. Relative proliferation compared to vehicle treated cells is shown. Data represents the average of three experiments±s.e.m. Significance was calculated using One-way analysis of variance (ANVA) and the Bonferroni correction. (****P⩽0.0001; ***P⩽0.001; **P⩽0.01). Concentrations used; 0.15 μM tofacitinib in combination with 3.75 μM selumetinib, 0.67 μM trametinib, 0.6 μM buparlisib and 0.3 μM tofacitinib in combination with 0.15 μM ABT-199.

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