HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells.

Abstract:

:Hypoxia-inducible factor-1α (HIF1α), a master transcriptional regulator of the cellular and systemic hypoxia response, is essential for the maintenance of self-renewal capacity of normal HSCs. It is still unknown whether HIF1α has a role in survival regulation of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). Using a mouse model of CML, here we report that HIF1α plays a crucial role in survival maintenance of LSCs. Deletion of HIF1α impairs the propagation of CML through impairing cell-cycle progression and inducing apoptosis of LSCs. Deletion of HIF1α results in elevated expression of p16(Ink4a) and p19(Arf) in LSCs, and knockdown of p16(Ink4a) and p19(Arf) rescues the defective colony-forming ability of HIF1α(-/-) LSCs. Compared with normal HSCs, LSCs appear to be more dependent on the HIF1α pathway. Together, these results demonstrate that HIF1α represents a critical pathway in LSCs and inhibition of the HIF1α pathway provides a therapeutic strategy for eradicating LSCs in CML.

journal_name

Blood

journal_title

Blood

authors

Zhang H,Li H,Xi HS,Li S

doi

10.1182/blood-2011-10-387381

subject

Has Abstract

pub_date

2012-03-15 00:00:00

pages

2595-607

issue

11

eissn

0006-4971

issn

1528-0020

pii

blood-2011-10-387381

journal_volume

119

pub_type

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