Both myeloproliferative disease and leukemia are induced by transplantation of bone marrow cells expressing v-myc.
An in vivo system has been established to investigate v-myc-induced hematopoietic neoplasia in mice. A Moloney murine leukemia virus (Mo-MLV)-derived recombinant retrovirus containing v-myc was used to infect immature bone marrow cells, and these cells were then transplanted into lethally irradiated recipients. All provirus-positive reconstituted mice were found to develop hematopoietic proliferative disorders and, in certain cases, overt leukemia--myeloblastic, myelomonocytic and T lymphocytic. In all cases expression of v-myc was high and the disease type did not correlate with the level of expression. We have isolated immortalized monocytes, myeloid progenitors and T lymphocytes from several of these mice and shown tumorigenicity in secondary syngeneic recipients. This system provides a model for investigating the progression from a pre-leukemic disease to malignancy. In addition, we describe a recombinant v-myc-containing retrovirus that directs high-level v-myc expression from the Mo-MLV promoter in all the hematopoietic cell types examined.
Bonham
L
L
Children's Medical Research Foundation, Sydney, New South Wales, Australia.
MacKenzie
K
K
Wood
S
S
Rowe
P B
PB
Symonds
G
G
D000818:Animals; D016026:Bone Marrow Transplantation; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D016259:Genes, myc; D007942:Leukemia, Experimental / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000209:etiology*; D011533:Proviruses / Q000235:genetics; D011995:Recombination, Genetic
D004279:DNA, Viral