Deletion of Cdc42 or Rac1 impair NPM-ALK lymphoma development in vivo. (A) Representative western blots of Cdc42 and Rac1 deletion in pretumoral thymuses obtained from wild-type (WT) or NPM-ALK transgenic mice. Mice were euthanized at 4 weeks of age when lymphoma was not phenotypically and morphologically detectable as previously described.¹²  Cell lysates were extracted and membranes were blotted with the indicated antibodies. (B) Representative western blots for Cdc42 and Rac1 deletion in primary tumors from mice with the indicated genotype. Three tumors out of 10 analyzed for each genotype are shown. (C-D) Kaplan-Meier survival curves of NPM-ALK transgenic mice in the presence or absence of Cdc42 and/or Rac1. NPM-ALK mice were crossed with mice carrying the indicated conditional knocked-in alleles. All mice were analyzed by necropsy to demonstrate the presence of lymphoma: NPM-ALK (n = 70), NPM-ALK;CD4Cre;Cdc42^fl/fl (NPM-ALK/Cdc42KO; n = 25), NPM-ALK;CD4Cre;Rac1^fl/fl (NPM-ALK/Rac1KO; n = 58), and NPM-ALK;CD4Cre;Cdc42^fl/fl;Rac1^fl/fl (NPM-ALK/Cdc42/Rac1KO; n = 17).