Induction of the erythropoietin receptor gene and acquisition of responsiveness to erythropoietin by stem cell factor in HML/SE, a human leukemic cell line.

The Journal of Biological Chemistry
T SatoT Nakahata

Abstract

HML/SE is a cytokine-dependent cell line established from childhood acute megakaryoblastic leukemia. Granulocyte-macrophage colony-stimulating factor or stem cell factor (SCF) alone could stimulate proliferation of HML/SE cells, however interleukin-3, interleukin-6, granulocyte colony-stimulating factor and thrombopoietin could not. Although erythropoietin (EPO) alone stimulated neither proliferation nor differentiation of HML/SE cells, it did stimulate proliferation of HML/SE cells and production of hemoglobin in the presence of SCF. SCF activated the human EPO receptor promoter and induced EPO receptor gene expression. Given these results, we speculate that HML/SE cells acquired responsiveness to EPO via the EPO receptor induced by SCF. Mutation analysis of putative transcription factor binding sites in the human EPO receptor promoter suggested that Sp1, rather than the GATA-1 binding site, contributed to the induction of the hEPOR gene. Although it is well documented that hematopoietic stem cells and primitive progenitors require both an early-acting cytokine and a lineage-specific cytokine to differentiate to a certain lineage, related mechanisms are not well understood. HML/SE may serve as an excellent model system to anal...Continue Reading

References

Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·L I ZonS H Orkin
Jul 1, 1996·International Journal of Hematology·A R MigliaccioG Migliaccio

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Citations

Dec 2, 2008·Expert Reviews in Molecular Medicine·Constance Tom NoguchiYi Jia
Apr 9, 2008·The Cancer Journal·Michael R Savona, Samuel M Silver
Apr 25, 2008·Critical Reviews in Oncology/hematology·Wolfgang JelkmannArthur J Sytkowski
Mar 23, 2005·Critical Reviews in Oncology/hematology·Veerendra Munugalavadla, Reuben Kapur
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masanari HasegawaHideoki Ogawa
Jan 17, 2002·Blood Reviews·M A SmithJ G Smith

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