Resistance to friend virus-induced erythroleukemia in W/W(v) mice is caused by a spleen-specific defect which results in a severe reduction in target cells and a lack of Sf-Stk expression.
The characteristic progression and specificity of Friend virus for the erythroid lineage have allowed for the identification of a number of host-encoded loci that are required for disease progression. Several of these loci, including the Friend virus susceptibility gene 2 (Fv2), dominant white spotting gene (W), and Steel gene (Sl), regulate the initial polyclonal expansion of infected erythroid progenitor cells. W and Sl encode the Kit receptor tyrosine kinase and its ligand, stem cell factor, respectively. W mutant mice are severely anemic, and earlier work suggested that this defect in erythroid differentiation is the cause for the resistance to Friend virus-induced erythroleukemia. Here we show that in bone marrow, W/W(v) mice have near normal numbers of target cells and the initial infection of bone marrow occurs normally in vivo. In contrast, spleen cells from W/W(v) mice infected both in vitro and in vivo with Friend virus failed to give rise to erythropoietin-independent colonies at any time following Friend virus infection, suggesting that mutation of the Kit receptor specifically affects target cells in the spleen, rendering the mutant mice resistant to the development of Friend virus-induced erythroleukemia. In addition, we show that the Kit+ pathogenic targets of Friend virus in the spleen are distinct from the pathogenic targets in bone marrow and this population of spleen target cells is markedly decreased in W/W(v) mice and these cells fail to express Sf-Stk. These results also underscore the unique nature of the spleen microenvironment in its role in supporting the progression of acute leukemia in Friend virus-infected mice.
Subramanian
Aparna
A
Graduate Program in Biochemistry, Microbiology and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Teal
Hami E
HE
Correll
Pamela H
PH
Paulson
Robert F
RF
D000818:Animals; D004921:Erythropoietin / Q000502:physiology; D005622:Friend murine leukemia virus / Q000472:pathogenicity* / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000821:virology*; D051379:Mice; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000235:genetics / Q000502:physiology
D004921:Erythropoietin; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases