Retrovirus-induced B cell neoplasia in the bursa of Fabricius.
The chicken bursa provides a revealing experimental model system which has helped unravel some of the mysteries surrounding induction of neoplasia by retroviruses lacking dominant viral oncogenes. Analysis of this system continues to provide opportunities for further insight into mechanisms underlying some of the essential characteristics of neoplastic change including maturation arrest, prolonged cell survival, and genetic instability. The deregulation of c-myc expression induced by nearby proviral integration appears to initiate preneoplastic change in a specific window of development, i.e., the bursal stem cell. The generation of large numbers of these preneoplastic stem cells, and the ability for further amplification by transplantation technology, may provide an opportunity to address questions such as how and why myc oncogenes produce preneoplastic maturation arrest or why stem cells are selective targets for these effects. Among the unexplained consequences of this preneoplastic state appears to be genetic instability which leads, inevitably, to formation of invasive bursal neoplasms. It is at least conceivable that the observed myc-induced enhancement of the remarkable capacity for apoptotic cell death present in bursal cells plays a role in this instability. DNA strand breakage is a very early feature of bursal cell apoptosis. If such breakage could occur in sublethal form it might provide a mechanism for increased frequency of genetic change (deletions, rearrangement, and recombination). Among the changes that seem required for successful tumor cell growth outside of follicles is the suppression of cell death induced by loss of cell-cell contact which is characteristic of normal and preneoplastic bursal cells. Several genes in the bcl-2 family are potentially important in the modulation of cell death events central to the evolution of these neoplasms. Their role, if any, remains to be established.
Neiman
P E
PE
Fred Hutchinson Cancer Research Center, University of Washington 98104.
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001353:Avian Leukosis / Q000276:immunology; D001354:Avian Leukosis Virus; D001402:B-Lymphocytes / Q000382:microbiology*; D002060:Bursa of Fabricius / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002645:Chickens / Q000382:microbiology*; D016259:Genes, myc / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000382:microbiology / Q000662:veterinary; D009857:Oncogenes / Q000235:genetics; D012192:Retroviridae Infections / Q000150:complications* / Q000662:veterinary