title: Erythroleukaemia induction by the Friend spleen focus-forming virus.
abstract: The Friend spleen focus-forming virus has been a valuable tool for understanding the molecular events involved in the multiple stages of leukaemia. As summarized in Figure 3, the primary effect of SFFV, which occurs within days, is to cause a polyclonal proliferation of erythroid precursor cells that can proliferate in the absence of their normal regulator erythropoietin. This is the direct result of the unique envelope glycoprotein encoded by SFFV, which is transported to the cell surface and apparently interacts with the EpoR or another component of the multimeric EpoR complex, resulting in the constitutive activation of the Epo signal transduction pathway. Within this proliferating population of erythroid cells is a rare cell that has undergone several genetic changes due to the integration of the viral genome in specific sites in the mouse DNA. This leads to the activation of a gene encoding the PU.1 transcription factor, whose high expression in erythroid cells may be the cause of the block in differentiation that is characteristic of SFFV-transformed erythroid cells. SFFV integration can also lead to the inactivation of the p53 tumour supressor gene, giving these cells a growth advantage in the mouse. The disease induced by SFFV in mice is very similar to polycythaemia vera in humans (Golde et al, 1981). The major clinical feature of polycythaemia vera is the continuous expansion of the number of mature red blood cells in the presence of low serum Epo levels. Also, BFU-E and CFU-E from these patients can form in the absence of Epo like the analogous cells from SFFV-infected mice (Casadevall et al, 1982). It is possible that haematopoietic cells from individuals suffering from this disease express a protein similar to the envelope glycoprotein of SFFV that can interact with the EpoR and lead to its constitutive activation. Alternatively, these patients may contain a mutant EpoR gene that is constitutively activated like the mutant EpoR described earlier. As we understand more fully how the SFFV envelope protein constitutively activates te EpoR complex, we can begin to design therapies to counteract its action that can then be applied to treating patients with polycythaemia vera or other human diseases associated with uncontrolled erythropoiesis.
authors.affiliation: Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research and Development Center MD 21702-1201, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Ruscetti
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000473:pathology / Q000821:virology; D004920:Erythropoiesis; D004921:Erythropoietin / Q000502:physiology; D005622:Friend murine leukemia virus / Q000235:genetics / Q000502:physiology; D015752:Genes, env; D016679:Genome, Viral; D006378:Helper Viruses / Q000235:genetics / Q000502:physiology*; D006965:Hyperplasia; D004915:Leukemia, Erythroblastic, Acute / Q000821:virology*; D007942:Leukemia, Experimental / Q000821:virology*; D051379:Mice; D016254:Mutagenesis, Insertional; D017467:Receptors, Erythropoietin / Q000502:physiology; D012192:Retroviridae Infections / Q000821:virology*; D015682:Retroviridae Proteins, Oncogenic; D015398:Signal Transduction; D013155:Spleen Focus-Forming Viruses / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014412:Tumor Virus Infections / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; D017467:Receptors, Erythropoietin; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C078780:glycoprotein gp55, Friend spleen focus-forming virus; C062022:v-Spi-1 protein, Friend spleen focus-forming virus; D004921:Erythropoietin