Skip to main content
Kent Academic Repository

Effects of Stem Cell Factor on Hypoxia-Inducible Factor 1 Alpha Accumulation in Human Acute Myeloid Leukaemia and LAD2 Mast Cells

Gibbs, Bernhard F., Yasinska, Inna M., Oniku, Abraham E., Sumbayev, Vadim V. (2011) Effects of Stem Cell Factor on Hypoxia-Inducible Factor 1 Alpha Accumulation in Human Acute Myeloid Leukaemia and LAD2 Mast Cells. PLoS ONE, 6 (7). e22502. ISSN 1932-6203. E-ISSN 1932-6203. (doi:10.1371/journal.pone.0022502) (KAR id:29574)


Stem cell factor (SCF) is a hematopoietic growth factor that exerts its activity by signalling through the tyrosine kinase receptor known as Kit or CD117. SCF-Kit signalling is crucial for the survival, proliferation and differentiation of hematopoietic cells of myeloid lineage. Furthermore, since myeloid leukaemia cells express the Kit receptor, SCF may play an important role in myeloid leukaemia progression too. However, the mechanisms of this pathophysiological effect remain unclear. Recent evidence shows that SCF triggers accumulation of the inducible alpha subunit of hypoxia-inducible factor 1 (HIF-1) in hematopoietic cells--a transcription complex that plays a pivotal role in cellular adaptation to low oxygen availability. However, it is unknown how SCF impacts on HIF-1? accumulation in human myeloid leukaemia and mast cells. Here we show that SCF induces HIF-1? accumulation in THP-1 human myeloid leukaemia cells but not in LAD2 mast cells. We demonstrated that LAD2 cells have a more robust glutathione (GSH)-dependent antioxidative system compared to THP-1 cells and are therefore protected against the actions of ROS generated in an SCF-dependent manner. BSO-induced GSH depletion led to a significant decrease in HIF-1? prolyl hydroxylase (PHD) activity in THP-1 cells and to near attenuation of it in LAD2 cells. In THP-1 cells, SCF-induced HIF-1? accumulation is controlled via ERK, PI3 kinase/PKC-?/mTOR-dependent and to a certain extent by redox-dependent mechanisms. These results demonstrate for the first time an important cross-talk of signalling pathways associated with HIF-1 activation--an important stage of the myeloid leukaemia cell life cycle.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0022502
Projects: The role of HIF-1 in IgE-mediated allergic responses of human basophils and mast cells
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
R Medicine > RC Internal medicine
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: [UNSPECIFIED] Asthma UK
Depositing User: Bernhard F. Gibbs
Date Deposited: 24 May 2012 09:12 UTC
Last Modified: 16 Nov 2021 10:07 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Gibbs, Bernhard F..

Creator's ORCID:
CReDIT Contributor Roles:

Sumbayev, Vadim V..

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.