Induction of granulocytic differentiation by 2 pathways

Pu Zhang, Erik Nelson, Hanna S. Radomska, Junko Iwasaki-Arai, Koichi Akashi, Alan D. Friedman, Daniel G. Jenen

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The CCAAT enhancer binding protein α (C/EBPα) transcription factor plays a critical role in granulocytopoiesis. Mice with a disruption of the C/EBPα gene demonstrate an early block in granulocytic differentiation, and disruption of C/EBPα function is a common theme in many types of human acute myelogenous leukemia, which is characterized by a block in myeloid development. To characterize further the nature of this block, we derived cell lines from the fetal liver of C/EBPα-deficient animals. These lines resembled morphologically the immature myeloid blasts observed in C/EBPα-/- fetal livers and did not express messenger RNA encoding early myeloid genes such as myeloperoxidase. Similarly, granulocytic markers such as Mac-1 and Gr-1 were not expressed; nor were erythroid and lymphoid surface antigens. Introduction of an inducible C/EBPα gene into the line revealed that conditional expression of C/EBPα induced the C/EBP family members C/EBPα and C/EBPε and subsequent granulocyte differentiation. Similar results were obtained when C/EBPα-/- cells were stimulated with the cytokines interleukin-3 and granulocyte-macrophage colony-stimulating factor, but not with all-trans retinoic acid, supporting a model of at least 2 pathways leading to the differentiation of myeloid progenitors to granulocytes and implicating induction of other C/EBP family members in granulopoiesis.

Original languageEnglish
Pages (from-to)4406-4412
Number of pages7
JournalBlood
Volume99
Issue number12
DOIs
Publication statusPublished - Jun 15 2002

Fingerprint

CCAAT-Enhancer-Binding Proteins
Genes
Liver
Granulocyte Precursor Cells
Interleukin-3
Surface Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Tretinoin
Granulocytes
Acute Myeloid Leukemia
Peroxidase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Zhang, P., Nelson, E., Radomska, H. S., Iwasaki-Arai, J., Akashi, K., Friedman, A. D., & Jenen, D. G. (2002). Induction of granulocytic differentiation by 2 pathways. Blood, 99(12), 4406-4412. https://doi.org/10.1182/blood.V99.12.4406

Induction of granulocytic differentiation by 2 pathways. / Zhang, Pu; Nelson, Erik; Radomska, Hanna S.; Iwasaki-Arai, Junko; Akashi, Koichi; Friedman, Alan D.; Jenen, Daniel G.

In: Blood, Vol. 99, No. 12, 15.06.2002, p. 4406-4412.

Research output: Contribution to journalArticle

Zhang, P, Nelson, E, Radomska, HS, Iwasaki-Arai, J, Akashi, K, Friedman, AD & Jenen, DG 2002, 'Induction of granulocytic differentiation by 2 pathways', Blood, vol. 99, no. 12, pp. 4406-4412. https://doi.org/10.1182/blood.V99.12.4406
Zhang P, Nelson E, Radomska HS, Iwasaki-Arai J, Akashi K, Friedman AD et al. Induction of granulocytic differentiation by 2 pathways. Blood. 2002 Jun 15;99(12):4406-4412. https://doi.org/10.1182/blood.V99.12.4406
Zhang, Pu ; Nelson, Erik ; Radomska, Hanna S. ; Iwasaki-Arai, Junko ; Akashi, Koichi ; Friedman, Alan D. ; Jenen, Daniel G. / Induction of granulocytic differentiation by 2 pathways. In: Blood. 2002 ; Vol. 99, No. 12. pp. 4406-4412.
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