Transcriptomics

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Expression profiling of primary leukemia initiating cell-enriched population induced by AML1-ETO9a


ABSTRACT: Combined gene expression and DNA occupancy profiling identifies JAK/STAT signaling as a valid therapeutic target of t(8;21) AML t(8;21) is commonly associated with acute myeloid leukemia (AML). The resulting AML1-ETO fusion proteins are involved in the pathogenesis of AML. To identify novel molecular and therapeutic targets, we performed combined gene expression and promoter occupancy profiling using a primary leukemia initiating cell-enriched population induced by AML1-ETO9a (AE9a). CD45, a negative regulator of cytokine/growth factor receptor and JAK/STAT signaling, is greatly downregulated; furthermore JAK1 and JAK2 are upregulated in these leukemia cells. Consequently, JAK/STAT signaling is enhanced in the AE9a leukemia cells. Importantly, AE9a leukemia cells are highly susceptible to perturbation of JAK/STAT signaling, and a JAK2-selective inhibitor, TG101209, effectively targets these leukemia cells in vivo, suggesting the potential efficacy of JAK2 inhibitors in treating t(8;21) AML. Wild-type or AE9a leukemic samples in triplicate.

ORGANISM(S): Mus musculus  

SUBMITTER: I-Ming Chen   Ming Yan  Luke F Peterson  Eun-Young Ahn  Dong-Er Zhang  Cheryl L Willman  Peter Hokland  Hans B Ommen  Miao-Chia Lo 

PROVIDER: E-GEOD-15195 | ArrayExpress | 2012-09-04

SECONDARY ACCESSION(S): GSE15195PRJNA116415

REPOSITORIES: GEO, ArrayExpress

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Chromosome translocation 8q22;21q22 [t(8;21)] is commonly associated with acute myeloid leukemia (AML), and the resulting AML1-ETO fusion proteins are involved in the pathogenesis of AML. To identify novel molecular and therapeutic targets, we performed combined gene expression microarray and promoter occupancy (ChIP-chip) profiling using Lin(-)/Sca1(-)/cKit(+) cells, the major leukemia cell population, from an AML mouse model induced by AML1-ETO9a (AE9a). Approximately 30% of the identified com  ...[more]

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