NPM-ALK Tg mice develop lymphomas.

Survival curves NPM-ALK Tg lines N16 (A) and N1(B). (C) Thymic lymphomas. Thymic lymphomas were composed of a homogeneous population of medium-sized lymphoid cells. Numerous mitosis and apoptotic bodies were present (left panel, × 100) (Ki67⁺ cells were documented by immunohistochemistry, insert; × 200). Immunohistochemical staining with anti-ALK Ab demonstrated a nuclear and cytoplasmic expression of the NPM-ALK fusion protein (right panel, × 100). (D) Typical phenotype of thymic lymphomas. Tumor cells obtained from neoplastic thymus were stained with the indicated Abs and analyzed (Thy1⁺, B220⁻, CD44⁺, CD8⁺, CD4^+/−, CD25⁻). (E) Southern blot analysis of NPM-ALK lymphomas showing a rearranged pattern of the T-cell receptor with all the enzymes used for digestion. Germline liver DNA was used as control. (F) NPM-ALK T-cell lines established tumors in immunodeficient mice. Tumor cells (2 × 10⁶) (NPM-ALK-Ova) were injected subcutis, and animals were followed daily for 4 weeks (upper panel). Tumors were composed of medium-sized blasts (lower panel, × 400) with high proliferation index (anti-Ki67 staining in the insert, × 200).