EXPRESSION AND DNA REARRANGEMENT OF PROTOONCOGENES IN CAS-BR-E-INDUCED NON-T-CELL NON-B-CELL LEUKEMIAS

The Cas-Br-E murine leukemia virus is a non-defective retrovirus that induces non-T-, non-B-cell leukemias in susceptible NIH/Swiss mice. A collection of tumors was examined for genomic DNA structure and RNA ex pression of known or putative proto-oncogenes and one tumor-suppressor gene, with the aim of identifying genes involved in Cas-Br-E-induced non-T-, non-B-cell leukemogenesis. Fli-1, p53, and Evi-1 were found to be rearranged in 72%, 23%, and 18% of the tumors, respectively, where as no DNA alteration were detected for c-myc, c-myb, Pim-1, Evi-2, and EpoR genes. Evi-1 rearrangements are rarely associated with p53 or Fl i-1 alterations. However, rearrangements of these last two genes are v ery often associated within the same tumor. Moreover, patterns of coor dinated expression of critical cell growth-regulating genes are consis tently associated with specific tumor types. These data suggest that C as-Br-E can induce two types of hematopoietic neoplasias by different mechanisms.