ETS-1 induces increased expression of erythroid markers in the pluripotent erythroleukemic cell lines K562 and HEL

Leukemia. 1997 Aug;11(8):1224-33. doi: 10.1038/sj.leu.2400735.


Members of the ETS gene family are known to be expressed in hematopoietic tissues and cell lines, and there is increasing evidence that ETS proteins may play a role in normal hematopoietic cell development. We demonstrate that ETS-1 can contribute to the development of an erythroid phenotype in vitro. The pluripotent erythroleukemic K562 and HEL cell lines express messages for a number of ETS genes, but only c-ETS-1 levels are elevated in response to treatment with hemin or cytosine arabinofuranoside (Ara-C), agents which induce erythroid differentiation. Furthermore, ETS-1 antisense oligonucleotides inhibit hemoglobinization of cells treated with Ara-C or hemin, and K562 and HEL cells infected with retrovirus expressing the c-ETS-1 gene exhibit a significant increase in erythroid character (as indicated by benzidine staining for hemoglobin (Hb) and surface marker analysis), a dramatic increase in responsiveness to hemin or Ara-C, and a decreased rate of proliferation (20-40% of control rates). In contrast, infection with virus expressing ETS-2 or vector sequences only causes no detectable changes in the proliferation or erythroid character of either the HEL or K562 cell lines. These data indicate a role for ETS-1 in erythroid differentiation.

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cytarabine / pharmacology
  • DNA-Binding Proteins*
  • Erythropoiesis* / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Hemin / pharmacology
  • Hemoglobins / biosynthesis
  • Humans
  • Leukemia, Erythroblastic, Acute / pathology*
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger / genetics
  • Repressor Proteins*
  • Trans-Activators / physiology*
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • ERF protein, human
  • ETS1 protein, human
  • ETS2 protein, human
  • Hemoglobins
  • Oligonucleotides, Antisense
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Cytarabine
  • Hemin