Bone marrow depletion by 89Sr complements a preleukemic defect in a long terminal repeat variant of Moloney murine leukemia virus.
We previously described a preleukemic state induced by Moloney murine leukemia virus (Mo-MuLV) characterized by hematopoietic hyperplasia in the spleen. Further experiments suggested that splenic hyperplasia results from inhibitory effects in the bone marrow, leading to compensatory extramedullary hematopoiesis. An enhancer variant of Mo-MuLV, Mo + PyF101 Mo-MuLV, fails to induce preleukemic hyperplasia and has greatly reduced leukemogenicity, indicating the importance of this state to efficient leukemogenesis. An alternative method for induction of preleukemic hyperplasia was sought. Treatment of mice with 89Sr causes specific ablation of bone marrow hematopoiesis and compensatory extramedullary hematopoiesis in spleen and nodes. NIH Swiss mice were inoculated neonatally with Mo + PyF101 Mo-MuLV and treated with 89Sr at 6 weeks of age. Approximately 85% developed lymphoid leukemia with a time course resembling that caused by wild-type Mo-MuLV. In contrast, very few animals treated with Mo + PyF101 Mo-MuLV or 89Sr alone developed disease. In approximately one-third of cases, the Mo + PyF101 Mo-MuLV proviruses were found at common sites for wild-type Mo-MuLV-induced tumors (c-myc, pvt-1, and pim-1), indicating that this virus is capable of performing insertional activation in T-lymphoid cells. These results support the proposal that splenic hyperplasia results from inhibitory effects in the bone marrow. They also indicate that Mo + PyF101 Mo-MuLV is blocked in early and not late events in leukemogenesis.
Li
Q X
QX
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Fan
H
H
D000818:Animals; D000831:Animals, Newborn; D015139:Blotting, Southern; D001853:Bone Marrow / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006411:Hematopoiesis, Extramedullary; D006965:Hyperplasia; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000382:microbiology / Q000473:pathology; D011289:Preleukemia / Q000382:microbiology* / Q000473:pathology; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D012091:Repetitive Sequences, Nucleic Acid; D013154:Spleen / Q000473:pathology; D013326:Strontium Radioisotopes
D004273:DNA, Neoplasm; D004279:DNA, Viral; D013326:Strontium Radioisotopes