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Ectopic expression of murine TPO receptor (c-mpl) in mice is pathogenic and
induces erythroblastic proliferation
L Cocault, D Bouscary, C Le Bousse Kerdiles, D Clay, F Picard, S Gisselbrecht and M Souyri
INSERM U 363, Institut Cochin de Genetique Moleculaire, Hopital Cochin,
Paris, France.
c-mpl, the cellular homologue of the v-mpl oncogene transduced in the
myeloproliferative leukemia virus (MPLV), encodes the receptor for
thrombopoietin, a cytokine involved in the proliferation and
differentiation of cells of the megakaryocytic lineage. Here, we show that
a retrovirus containing murine c-mpl cDNA (HSFmmpl) is pathogenic in vivo
when inoculated in adult mice. All mice developed hepatosplenomegaly and
died within 9 to 12 weeks after infection. Histological analysis showed
that spleen, liver, and peripheral blood were invaded by erythroblasts at
every stage of differentiation. In contrast to the myeloproliferative
syndrome induced by MPLV, we did not observe an infiltration of these
organs with cells from the granulocytic lineage nor a thrombocytosis. In
fact, the platelet count of HSFmmpl mice progressively decreased and a
severe thrombocytopenia was observed late in the course of the disease.
Further characterization of the target progenitor of HSFmmpl virus in the
spleen and bone marrow of diseased animals was accomplished using in vitro
clonogenic progenitor cell assays. This analysis indicated that both late
and early erythroid compartment (colony-forming unit- erythroid and
burst-forming unit-erythroid) were largely increased in the spleens. The
colony-forming unit-granulocyte-macrophage compartment was also increased
but to a lesser extent. This study shows for the first time that ectopic
expression of a member of the cytokine receptor superfamily promotes
hematopoietic progenitor cell proliferation and could play a role in
leukemogenesis.
Volume 88,
Issue 5,
pp. 1656-1665,
09/01/1996
Copyright © 1996 by The American Society of Hematology
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