Role of transcription factors C/EBPα and PU.1 in normal hematopoiesis and leukemia

Steffen Koschmieder, Frank Rosenbauer, Ulrich G. Steidl, Bronwyn M. Owens, Daniel G. Tenen

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Differentiation of hematopoietic stem and progenitor cells is under strict control of a regulatory network orchestrated by lineage-specific transcription factors. A block in normal differentiation is a major contributing factor in the development of solid tumors and leukemias. Cells from patients with acute myeloid leukemia (AML) frequently harbor mutated or dysregulated transcription factor genes, suggesting their involvement in leukemogenesis. As a consequence, these alterations diminish the pool of available molecules of a small number of critical transcription factors, such as CCAAT enhancer binding proteins, PU.1, GATA-1, and AML-1. In this review, we focus on the mechanisms of how this functional pool of transcription factors is maintained during normal and malignant hematopoiesis, including direct protein-protein interactions, competition for DNA binding, and the control of transcription factor genes by proximal and distal regulatory elements. Results of recent studies of mice carrying hypomorphic PU.1 alleles have indicated that reduction in the expression of a single transcription factor is capable of predisposing mice to AML. The implications of these findings for the study of hematopoiesis in the future as well as novel approaches to more disease-specific therapies are discussed.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
JournalInternational Journal of Hematology
Volume81
Issue number5
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Hematopoiesis
Leukemia
Transcription Factors
Acute Myeloid Leukemia
Hematopoietic Stem Cells
CCAAT-Enhancer-Binding Proteins
Genes
Proteins
Alleles
DNA
Neoplasms

Keywords

  • C/EPBα
  • Hematopoiesis
  • Leukemia
  • PU.1
  • Transcription factors

ASJC Scopus subject areas

  • Hematology

Cite this

Role of transcription factors C/EBPα and PU.1 in normal hematopoiesis and leukemia. / Koschmieder, Steffen; Rosenbauer, Frank; Steidl, Ulrich G.; Owens, Bronwyn M.; Tenen, Daniel G.

In: International Journal of Hematology, Vol. 81, No. 5, 06.2005, p. 368-377.

Research output: Contribution to journalArticle

Koschmieder, Steffen ; Rosenbauer, Frank ; Steidl, Ulrich G. ; Owens, Bronwyn M. ; Tenen, Daniel G. / Role of transcription factors C/EBPα and PU.1 in normal hematopoiesis and leukemia. In: International Journal of Hematology. 2005 ; Vol. 81, No. 5. pp. 368-377.
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