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F Wendling, JF Penciolelli, M Charon and P Tambourin
Laboratoire Immunologie et Oncologie des Maladies Retrovirales, INSERM
U152, Paris, France.
The myeloproliferative leukemia virus (MPLV), a novel murine retroviral
complex that does not transform fibroblasts, has been shown to cause an
acute leukemia in adult mice accompanied by a progressive polycythemia. The
present study demonstrates that, on in vivo inoculation, MPLV induces a
rapid suppression of growth factor requirement for in vitro colony
formation by both the late and the primitive erythroid progenitor cells.
CFU-e-derived erythrocytic colonies developed and differentiated in
semi-solid medium without the addition of erythropoietin (Epo). In
addition, the formation of CFU-e colonies was not altered by the presence
of specific neutralizing Epo antibodies. In the spleen, the CFU-e pool size
increased rapidly up to 30-fold. By day 6 postinfection, 100% of these
progenitor cells were Epo-independent. The in vivo effects of
MPLV-infection on early erythroid progenitor cell compartments were
examined in cultures grown for seven days. The concentration of erythroid
progenitor cells was twofold elevated in spleen from MPLV-infected mice. As
early as day 4 postinfection, 50% of these progenitors produced fully
hemoglobinized colonies in serum-free cultures without the addition of
interleukin-3 (IL-3) and Epo. Most spontaneous colonies were large and
contained up to 10(5) cells per colony. They were composed of either
erythroblasts only (16%) or erythroblasts and megakaryocytes (70%); few of
them were multipotential (14%). In the marrow, the total number of BFU-e
was reduced and only few factor-independent bursts were observed,
suggesting a rapid migration of infected progenitors from marrow to spleen.
Furthermore, the data show that abnormal erythropoiesis was due to the
replication defective MPLV information and was not influenced by the Fv-2
locus.
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| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||