Journal article

HIF-1 alpha is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1 alpha

CE Forristal, B Nowlan, RN Jacobsen, V Barbier, G Walkinshaw, CR Walkley, IG Winkler, JP Levesque

LEUKEMIA | NATURE PUBLISHING GROUP | Published : 2015

Abstract

Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in ..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Health and Medical Research Council


Funding Acknowledgements

This work was supported by project grants 604303 and 1061333 from the National Health and Medical Research Council of Australia. CRW is the Phillip Desbrow Senior Research Fellow of the Leukaemia Foundation of Australia. IGW and JPL are supported by Career Development Fellowships (4888817 and 1033736) and Senior Research Fellowship (1044091) respectively from the National Health and Medical Research Council.