Induction of CCAAT/enhancer binding protein-delta by cytokinins, but not by retinoic acid, during granulocytic differentiation of human myeloid leukaemia cells

Br J Haematol. 2005 Feb;128(4):540-7. doi: 10.1111/j.1365-2141.2004.05326.x.


Cytokinins, purine derivatives that act as hormones to control many processes in plants, are very effective at inducing the granulocytic differentiation of human myeloid leukaemia cells. Isopentenyladenine (IPA), a potent cytokinin, significantly induced the expression of CCAAT/enhancer-binding protein (C/EBP)delta, but not C/EBP alpha protein, whereas all-trans retinoic acid, a well-known inducer of granulocytic differentiation, induced C/EBP alpha but not C/EBP delta protein. Antisense oligonucleotide for C/EBP delta, but not C/EBP alpha or C/EBP beta, effectively suppressed IPA-induced differentiation, suggesting that the expression of C/EBP delta protein is necessary for cytokinin-induced differentiation. Although C/EBP alpha is known to be crucial for granulocytic differentiation, the function of C/EBP delta has not been well documented in the regulation of haematopoiesis. The role of C/EBP delta in the granulocytic differentiation of myeloid leukaemia cells is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • CCAAT-Enhancer-Binding Protein-delta
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • CCAAT-Enhancer-Binding Proteins / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cytokinins / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Granulocytes / metabolism*
  • Granulocytes / pathology
  • HL-60 Cells
  • Humans
  • Isopentenyladenosine
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / metabolism*
  • Leukemia, Promyelocytic, Acute / pathology
  • Oligonucleotides, Antisense / pharmacology
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • CEBPD protein, human
  • Cytokinins
  • Oligonucleotides, Antisense
  • Transcription Factors
  • CCAAT-Enhancer-Binding Protein-delta
  • N(6)-(delta(2)-isopentenyl)adenine
  • Tretinoin
  • Isopentenyladenosine
  • Adenine