Effect of transcription-factor concentrations on leukemic stem cells

Frank Rosenbauer, Steffen Koschmieder, Ulrich G. Steidl, Daniel G. Tenen

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Increasing evidence suggests that leukemias are sustained by leukemic stem cells. However, the molecular pathways underlying the transformation of normal cells into leukemic stem cells are still poorly understood. The involvement of a small group of key transcription factors into this process was suggested by their frequent mutation or down-regulation in patients with acute myeloid leukemia (AML). Recent findings in mice with hypomorphic transcription-factor genes demonstrated that leukemic stem-cell formation in AML could directly be caused by reduced transcription-factor activity beyond a critical threshold. Most interestingly, those experimental models and the paucity of biallelic null mutations or deletions in transcription-factor genes in patients suggest that AML is generally associated with graded down-regulation rather than complete disruption of transcription factors. Here, we discuss the effects of transcription-factor concentrations on hematopoiesis and leukemia, with a focus on the regulation of transcription-factor gene expression as a major mechanism that alters critical threshold levels during blood development and cancer.

Original languageEnglish (US)
Pages (from-to)1519-1524
Number of pages6
JournalBlood
Volume106
Issue number5
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

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Stem cells
Transcription Factors
Stem Cells
Acute Myeloid Leukemia
Leukemia
Down-Regulation
Genes
Sequence Deletion
Hematopoiesis
Gene expression
Blood
Theoretical Models
Cells
Gene Expression
Mutation
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Effect of transcription-factor concentrations on leukemic stem cells. / Rosenbauer, Frank; Koschmieder, Steffen; Steidl, Ulrich G.; Tenen, Daniel G.

In: Blood, Vol. 106, No. 5, 01.09.2005, p. 1519-1524.

Research output: Contribution to journalArticle

Rosenbauer, F, Koschmieder, S, Steidl, UG & Tenen, DG 2005, 'Effect of transcription-factor concentrations on leukemic stem cells', Blood, vol. 106, no. 5, pp. 1519-1524. https://doi.org/10.1182/blood-2005-02-0717
Rosenbauer, Frank ; Koschmieder, Steffen ; Steidl, Ulrich G. ; Tenen, Daniel G. / Effect of transcription-factor concentrations on leukemic stem cells. In: Blood. 2005 ; Vol. 106, No. 5. pp. 1519-1524.
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