Granulocyte colony-stimulating factor receptor mRNA upregulation is an immediate early marker of myeloid differentiation and exhibits dysfunctional regulation in leukemic cells.
The identification of early markers of myeloid differentiation can facilitate an understanding of how differentiation is arrested in leukemogenesis. Using murine bone marrow and the granulocyte-precusor cell line 32Dc13, we show that message for the granulocyte colony-stimulating factor receptor (G-CSFR) is upregulated by G-CSF in an immediate early fashion that is specific to the differentiation pathway and is antagonized by interleukin-3. We further show that G-CSFR message is superinduced by cycloheximide and that these patterns of regulation are altered in leukemic cell lines. In particular, the v-abl oncogene product supresses both ligand-mediated upregulation and superinduction of the G-CSFR gene.
Steinman
R A
RA
Department of Medicine, University of Pittsburgh School of Medicine, PA.
Tweardy
D J
DJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D015973:Gene Expression Regulation, Leukemic; D016313:Genes, abl; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D015854:Up-Regulation
D007377:Interleukin-3; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor