Novel insights into the pathogenesis of the Graffi murine leukemia retrovirus.
The Graffi murine leukemia virus (MuLV) was isolated in 1954 by Arnold Graffi, who characterized it as a myeloid leukemia-inducing retrovirus. He and his team, however, soon observed the intriguing phenomenon of hematological diversification, which corresponded to a decrease of myeloid leukemias and an increase of other types of leukemias. Recently, we derived two different molecular clones corresponding to ecotropic nondefective genomes that were named GV-1.2 and GV-1.4. The induced leukemias were classified as myeloid based on morphological analysis of blood smears. In this study, we further characterized the two variants of the Graffi murine retrovirus, GV-1.2 and GV-1.4, in three different strains of mice. We show that the Graffi MuLV is a multipotent retrovirus capable of inducing both lymphoid (T- and B-cell) and nonlymphoid (myeloid, erythroid, megakaryocytic) leukemia. Many of these are very complex with concomitant expression of different hematopoietic lineages. Interestingly, a high percentage of megakaryocytic leukemias, a type of leukemia rarely observed with MuLVs, arise in the FVB/n strain of mice. The genetic backgrounds of the different strains of mice influence greatly the results. Furthermore, the enhancer region, different for GV-1.2 and GV-1.4, plays a pivotal role in the disease specificity: GV-1.2 induces more lymphoid leukemias, and GV-1.4 induces more nonlymphoid ones.
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Case Postale 8888 Succ. Centre-ville, Montréal, Canada H3C-3P8.
Véronique
V
Voisin
Corinne
C
Barat
Trang
T
Hoang
Eric
E
Rassart
D000818:Animals; D004742:Enhancer Elements, Genetic; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000473:pathology; D007942:Leukemia, Experimental / Q000473:pathology; D007947:Leukemia, Megakaryoblastic, Acute / Q000276:immunology / Q000473:pathology; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology; D015458:Leukemia, T-Cell / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012192:Retroviridae Infections / Q000473:pathology; D020079:Terminal Repeat Sequences; D014412:Tumor Virus Infections / Q000473:pathology; D017735:Virus Latency