@Article{ecn.2010.0204,
AUTHOR = {Kimberley Joanne Hatfield, Siv Lise Bedringsaas, Anita Ryningen, Bjørn Tore Gjertsen, Øystein Bruserud},
TITLE = {Hypoxia increases HIF-1α expression and constitutive cytokine release by primary human acute myeloid leukaemia cells},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {3},
PAGES = {154--164},
URL = {http://www.techscience.com/ECN/v21n3/65853},
ISSN = {1952-4005},
ABSTRACT = {Introduction. Low oxygen tension is able to modulate the expression of several genes involved in
physiological and pathological processes. A major regulator of gene expression is the heterodimeric transcrip
tion factor hypoxia inducible factor-1 (HIF-1), which also regulates angiogenesis-related genes, including the
protein expression of angioregulatory cytokines. Angiogenesis has been shown to play a role in haematological
disorders, and low oxygen tension might thereby influence leukaemogenesis and chemosensitivity in human
acute myeloid leukaemia (AML). Methods. We examined the effect of a hypoxic environment (1% O<sub>2</sub>) on
in vitro-cultured, primary human AML cells with regard to HIF-1α expression, colony formation and cytokine
release. Results. Our study demonstrated that hypoxic culture conditions increased HIF-1α expression in pri
mary AML cells for a majority of the investigated patients when compared to culture at atmospheric (21%)
oxygen tension. Hypoxia also increased the release of vascular endothelial growth factor (VEGF), osteopontin,
as well as several CCL- (CCL3/4/5/7/8) and CXCL-chemokines (CXCL1 and proangiogenic CXCL8) by AML
cells. The constitutive release of antiangiogenic CXCL9-11 was not altered by the low oxygen tension. The wide
variation between patients as regards the release of the various cytokines persisted during hypoxia. Conclusion.
Culture of primary AML cells under low oxygen tension induces HIF-1α expression and increases the release of
several cytokines, including proangiogenic mediators, compared to culture at ambient 21% O<sub>2</sub>.},
DOI = {10.1684/ecn.2010.0204}
}