Lymphoma and cutaneous disease regression on ALK oncogene inactivation in TPM3-ALK mice. Clinical examination and autopsy findings show that all animals with fully developed disease (TPM3-ALK ON; n=10) presented with disseminated lymphoma with lymph node and spleen enlargement and skin nodules mostly related to keratoacanthoma-like lesions involving the skin, snout, and paws (TPM3-ALK ON: A,C,E,G,I). Ten additional moribund mice were treated with Dox in drinking water (100 μg/mL) and 1 intraperitoneal injection of 100 μL of Dox solution (100 μg/mL; TPM3-ALK OFF; B,D,F,H,J). Compared with the ON mice, the OFF mice exhibited, after 12 days of Dox treatment, a major clearing of the skin lesions (A,C vs B,D) associated with the regrowth of hair within 3 weeks, a regression of spleen and lymph node enlargement (G vs H), and an ALK oncogene expression down-regulation as assessed by anti-ALK immunostaining (E,I vs F,J) and Western blotting analysis (K lane ON vs OFF). Note, in panel K, a vertical line has been inserted to indicate a repositioned gel lane. In panel F, apoptotic ALK-positive cells admixed with exfoliated material (arrow). Original magnifications ×50 (C-F) and ×640 (I-J).