Murine erythroid cell lines derived with c-myc retroviruses respond to leukemia-inhibitory factor, erythropoietin, and interleukin 3.
The transforming potential of the c-myc gene is shown here, for the first time, to include murine erythroid cells. Continuously growing cell lines were reproducibly generated by infection of day 13 CBA fetal liver cells with novel recombinant c-myc retroviruses. By cytostaining, most cells resembled early erythroblasts, but certain lines also contained significant numbers of hemoglobinized cells. RNA analysis revealed substantial expression of the genes encoding beta-globin and the erythroid-specific transcription factor GF-1. Although apparently immortal, the lines were not initially transplantable. Thus, constitutive myc expression in early erythroid cells can enhance their self-renewal capacity but is insufficient to fully transform them. The cell lines proliferated without the addition of exogenous factors, but their clonogenicity in semisolid medium was enhanced in the presence of erythropoietin, interleukin 3, and/or leukemia-inhibitory factor. In combination with either interleukin 3 or erythropoietin, leukemia-inhibitory factor also facilitated differentiation of certain lines. These results suggest that leukemia-inhibitory factor may have a previously unsuspected role in the regulation of erythropoiesis and could be considered as a possible therapeutic agent for the clinical management of erythroleukemia.
Cory
S
S
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Maekawa
T
T
McNeall
J
J
Metcalf
D
D
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002472:Cell Transformation, Viral; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016259:Genes, myc; D005914:Globins / Q000096:biosynthesis / Q000378:metabolism; D006131:Growth Inhibitors; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008099:Liver / Q000166:cytology / Q000196:embryology; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D012190:Retroviridae / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D006131:Growth Inhibitors; D007377:Interleukin-3; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D014157:Transcription Factors; D004921:Erythropoietin; D005914:Globins