Characterization of a preleukemic state induced by Moloney murine leukemia virus: evidence for two infection events during leukemogenesis.
A preleukemic state in mice inoculated with Moloney murine leukemia virus (Mo-MuLV) was characterized. Six to 10 weeks after neonatal inoculation, animals developed mild splenomegaly and generalized hematopoietic hyperplasia. The hyperplasia was evident from myeloid and erythroid progenitor assays. A nonleukemogenic variant, Mo+PyF101 Mo-MuLV, did not induce the hyperplasia; this suggests that the hyperplasia is a necessary event in Mo-MuLV leukemogenesis. Another variant, MF-MuLV, which contains the long terminal repeat of Friend MuLV and causes erythroid leukemia instead of T-cell lymphoma, also induced the preleukemic hyperplasia. A model for Mo-MuLV leukemogenesis is presented in which two infection events are necessary: the first leads to generalized hematopoietic hyperplasia, and the second results in site-specific insertion and long terminal repeat activation of cellular protooncogenes.
D000818:Animals; D000831:Animals, Newborn; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D005622:Friend murine leukemia virus / Q000235:genetics; D005786:Gene Expression Regulation; D006965:Hyperplasia; D004915:Leukemia, Erythroblastic, Acute / Q000209:etiology*; D007942:Leukemia, Experimental / Q000209:etiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008979:Moloney murine leukemia virus / Q000472:pathogenicity*; D011289:Preleukemia / Q000209:etiology* / Q000473:pathology; D011519:Proto-Oncogenes; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology; D013950:Thymus Gland / Q000473:pathology