Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling in BCR/ABL-expressing LSCs and BCR/ABL-expressing Hif1a-/-LSCs


ABSTRACT: Using a mouse model of chronic myelogenous leukemia (CML), here we report that HIF1M-NM-1 plays a crucial role in survival maintenance of leukemia stem cells (LSCs). Deletion of HIF1M-NM-1 impairs the propagation of CML through impairing cell cycle progression and inducing apoptosis of LSCs. Deletion of HIF1M-NM-1 results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1M-NM-1-/- LSCs. To further identify the pathways in which Hif1a regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Hif1a-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+ cells, BCR-ABL-expressing wild type LSCs, and BCR-ABL-expressing Hif1a-/- LSCs. To identify genes that are regulated by BCR-ABL in LSCs and LSCs without the Hif1a gene, we compared the gene profile between wild type (WT) LSCs and Hif1a-/- LSCs.

ORGANISM(S): Mus musculus

SUBMITTER: shaoguang li 

PROVIDER: E-GEOD-35111 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Zhang Haojian H   Li Huawei H   Xi Hualin S HS   Li Shaoguang S  

Blood 20120124 11


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  ...[more]

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