Phenotyping of Evi1, Evi11/Cb2, and Evi12 transformed leukemias isolated from a novel panel of Cas-Br-M murine leukemia virus-infected mice

Cas-Br-M murine leukemia virus (MULV) is a slow-transforming retrovirus tha t potently induces leukemias in mice and therefore is well suited for retro viral insertional mutagenesis. We used Cas-Br-M MuLV in NIH/Swiss mice to e stablish a new panel of mainly myeloid leukemias. All tumors found in leuke mic animals were classified by gross pathology, morphology, and immunopheno type, as well as the incidence of known common virus integration sites (VIS s) in MuLV-induced myeloid malignancies (i.e., Evi1, Evi11/Cb2 Evi12, Fli1, and c-Myb). Interestingly, male mice were more susceptible than females to the induction of leukemia by Cas-Br-M MuLV. Seventy-four of the Cas-Br-M M uLV-inoculated mice developed a severe splenomegaly, sometimes in associati on with a thymoma. Although most of the immunophenotyped Cas-Br-M MuLV tumo rs were of myeloid origin (58%), numerous T-cell leukemias (21%) and mixed myeloid/T-cell leukemias (21%) were found. The myeloid leukemias and myeloi d compartment of the mixed leukemias were further characterized by immunoph enotyping with stem cell-, myeloid-, and erythroid-specific antibodies. The known Cas-Br-M MuLV common VISs (Evi1, Evi11/C62, and Evi12) were demonstr ated in 19%, 12%, and 20% of the cases. respectively, whereas no Fli1 and c -Myb rearrangements were found. Integrations into Evi1 were restricted to m yeloid leukemias, whereas those in Evi11/Cb2 and Evi12 were identified in m yeloid as well as T-lymphoid leukemias. This panel of well characterized Ca s-Br-M MuLV-induced hematopoietic tumors may be useful for the isolation an d characterization of new proto-oncogenes involved in myeloid or T-cell leu kemias. (C) 2000 Academic Press.