Fig 1: Activating ALK mutation F1174L influences impact of LCL161 and chemotherapy in neuroblastomaALK status (ALKwt vs. ALKF1174L) was correlated to combination index (CI) scores reflecting synergistic (CI < 1) or additive/antagonistic (CI = 1) interaction of chemotherapeutic drugs with LCL161 A.. Box plots represent the interquartile range (25-75th percentile) and the median value (black line). Whiskers represent the maximum and minimum values, respectively. Proliferation of cells treated with the indicated concentrations of TAE684 was determined after 48h B.. Proliferation of untreated cells was defined as 100%. Cells were treated with the indicated concentrations of doxorubicin, LCL161 or TAE684 and inhibition of proliferation was determined after 48h C.. Inhibition of proliferation of untreated cells was defined as 0%. IC50 values for dose-effect curves were determined and taken as a basis for the calculation of combination indices (CI) D.. SH-EP TET21N cells were treated with the indicated concentrations of doxorubicin, LCL161 or TAE684 and the proportion of apoptotic cells was determined by flow cytometry (Annexin V and PI staining) after 48 h E.. Dot plots are representative for the performed analyses. Values represent the mean ± SD of three independent experiments B.-E., *; p = 0.05.