Factor-independent erythropoietic progenitor cells in leukemia induced by the myeloproliferative leukemia virus.
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.
Wendling
F
F
Laboratoire Immunologie et Oncologie des Maladies Rétrovirales, INSERM U152, Paris, France.
Penciolelli
J F
JF
Charon
M
M
Tambourin
P
P
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004920:Erythropoiesis; D004921:Erythropoietin / Q000276:immunology / Q000502:physiology*; D006378:Helper Viruses / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D007106:Immune Sera / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000502:physiology; D007942:Leukemia, Experimental / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009500:Neutralization Tests; D013154:Spleen / Q000473:pathology; D014410:Tumor Stem Cell Assay
D007106:Immune Sera; D004921:Erythropoietin