GSBS Student Publications


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

Student Author(s)

Haojian Zhang

GSBS Program

Cancer Biology

UMMS Affiliation

Department of Medicine, Division of Hematology/Oncology; Department of Biochemistry and Molecular Pharmacology



Document Type


Medical Subject Headings

Animals; Anoxia; Apoptosis; Biological Markers; Blotting, Western; Bone Marrow Transplantation; Cell Cycle; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p16; Flow Cytometry; Gene Expression Profiling; Hypoxia-Inducible Factor 1, alpha Subunit; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplastic Stem Cells; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Survival Rate


Cancer Biology | Hematology


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.

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Citation: Blood. 2012 Mar 15;119(11):2595-607. Epub 2012 Jan 24. doi: 10.1182/blood-2011-10-387381

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