Concise review

Genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells

Deniz Gezer, Milica Vukovic, Tomoyoshi Soga, Patrick J. Pollard, Kamil R. Kranc

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. Stem Cells 2014;32:1390-1397

Original languageEnglish
Pages (from-to)1390-1397
Number of pages8
JournalStem Cells
Volume32
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Hematopoietic Stem Cells
Dissection
Stem Cells
Hematopoiesis
Multipotent Stem Cells
Stem Cell Niche
Adult Stem Cells
Hypoxia
Leukemia
Maintenance

Keywords

  • Acute myeloid leukemia
  • Cited2
  • Hematological malignancies
  • Hematopoietic progenitors
  • Hematopoietic stem cells
  • HIF-1
  • HIF-2
  • Hypoxia

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Concise review : Genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells. / Gezer, Deniz; Vukovic, Milica; Soga, Tomoyoshi; Pollard, Patrick J.; Kranc, Kamil R.

In: Stem Cells, Vol. 32, No. 6, 2014, p. 1390-1397.

Research output: Contribution to journalArticle

Gezer, Deniz ; Vukovic, Milica ; Soga, Tomoyoshi ; Pollard, Patrick J. ; Kranc, Kamil R. / Concise review : Genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells. In: Stem Cells. 2014 ; Vol. 32, No. 6. pp. 1390-1397.
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