title: TEL/ETV6 accelerates erythroid differentiation and inhibits megakaryocytic maturation in a human leukemia cell line UT-7/GM.
abstract: TEL/ETV6 accelerates erythroid differentiation in the murine erythroleukemia cell line. To clarify the effects of TEL on megakaryocytic maturation as well as erythroid differentiation, we chose the human leukemia cell line UT-7/GM that differentiates into the erythroid and megakaryocytic lineages by treatment with erythropoietin and thrombopoietin, respectively. Upon erythropoietin exposure, overexpressed TEL stimulated hemoglobin synthesis and accumulation of the erythroid differentiation-specific transcripts such as gamma-globin, delta-aminolevulinic acid synthase-erythroid, and erythropoietin receptor. Moreover, the glycophorin A(+)/glycoprotein IIb(-) fraction appeared more rapidly in the TEL-overexpressing cells. Interestingly, overexpression of TEL was associated with lower levels of the megakaryocytic maturation-specific glycoprotein IIb and platelet factor 4 transcripts under the treatment with thrombopoietin. Consistently, the glycophorin A(-)/glycoprotein IIb(+) fraction increased more slowly in the TEL-overexpressing cells. Finally, expression of endogenous TEL proteins in UT-7/GM cells was down-regulated following erythropoietin and thrombopoietin exposure. All these data suggest that TEL may decide the fate of human erythrocyte/megakaryocyte common progenitors to differentiate towards the erythroid lineage and against the megakaryocytic lineage.
authors.affiliation: Department of Hematology, Dokkyo University School of Medicine, 880 Kitakobayashi, Shimotsuga-gun, Tochigi 321-0293, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Takahashi
authors.forename: Ko
authors.initials: K
authors.lastname: Sasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Kvomatsu
authors.forename: Kinuko
authors.initials: K
authors.lastname: Mitani
mesh_terms: D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D004912:Erythrocytes / Q000502:physiology; D004921:Erythropoietin / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008533:Megakaryocytes / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000502:physiology*; D013926:Thrombopoietin / Q000502:physiology; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D004921:Erythropoietin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D013926:Thrombopoietin; D000097764:ETS Translocation Variant 6 Protein