STAT1 signaling is functionally intact in ALK+ ALCL. (A) IFN-γ triggered STAT1 phosphorylation and increased the expression of IRF-1 (a STAT1 downstream target) in SupM2 and Karpas 299 cells. STAT1 was not changed in this time frame. (B) Western blots showed that STAT1 was activated and phosphorylated in response to IFN-γ stimulation in a dose-dependent manner for 24 hours. The downstream target IRF-1 also increased with IFN-γ stimulation. The cleaved poly (ADP-ribose) polymerase (PARP) was blotted, and it increased in a dose-dependent manner in response to IFN-γ at 24 hours. (C) Using trypan blue exclusion assay, we found that IFN-γ significantly decreased cell growth in both ALK+ ALCL cell lines in a dose-dependent manner. (D) By using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, or MTS assay, we found that IFN-γ synergized with crizotinib in suppressing cell growth in both ALK+ ALCL cell lines. (E-F) Karpas 299 cells transfected with STAT1C-flag showed a significant accumulation of the sub G₀→G₁ fraction. Statistical significance was calculated by Student t test. *P < .05; **P < .01.