ICOS expression is induced by NPM-ALK. (A) Dose- and time-dependent inhibition of NPM-ALK enzymatic activity by the small-molecule ALK inhibitor (ALKi) CEP-26939 as identified in Western blot using phospho-ALK-specific antibody in the ALK⁺ TCL cell line SUDHL-1 with the ALK- TCL cell line 2B serving as a negative control. (B-D) Effect of ALK inhibition on ICOS expression. The depicted ALK⁺ TCL cell lines were examined by flow cytometry for ICOS expression after treatment with 2 different ALK inhibitors (ALKi), CEP-26939¹⁵  (B) and CEP-14513,¹⁸  (C) at the indicated concentrations. The ALK-inactive, CEP-14153-related CEP-11988 compound²²  served as a negative control. The effect of 100nM CEP-26939 on expression of ICOS mRNA was also determined (D). (E) Effect of siRNA-mediated NPM-ALK depletion on expression of ICOS in the 2 depicted ALK⁺ TCL cell lines. (B-E) The numbers in parentheses indicate the percentage of ICOS expression inhibition relative to controls.