Interferon-alpha inhibits erythropoietin-induced proliferation, but not differentiation, and restricts erythroleukemia development.
The immature erythroid cell line J2E responds to erythropoietin (Epo) by proliferating and terminally differentiating into hemoglobin-synthesizing red blood cells. These cells produce a rapid, fatal erythroleukemia in mice characterized by hepatosplenomegaly and severe anemia. The aim of this study was to investigate the effects of murine interferons-alpha (MuIFN-alpha) on J2E cells in vitro and in vivo. Here we show that in culture MuIFN-alpha inhibited the Epo-induced proliferation of J2E cells but did not interfere with differentiation. When mice with J2E erythroleukemias were treated with MuIFNs in vivo, an extension of their life span was observed. Moreover, numerous necrotic lesions of infiltrating leukemic cells were detected in the spleens of these mice. Finally, ex vivo treatment of leukemic bone marrow cells with Epo and MuIFNs delayed mortality even further. It was concluded that MuIFNs (1) suppressed the proliferation of J2E cells in vitro but did not affect Epo-induced differentiation, and (2) inhibited the progress of erythroleukemias, especially in combination with Epo.
Lai
C M
CM
Department of Microbiology, University of Western Australia, Nedlands.
Swaminathan
N
N
Beilharz
M W
MW
Papadimitriou
J
J
Klinken
S P
SP
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004351:Drug Resistance; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology; D004921:Erythropoietin / Q000037:antagonists & inhibitors*; D005260:Female; D016898:Interferon-alpha / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009336:Necrosis; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D016898:Interferon-alpha; D004921:Erythropoietin