SYK Is a Critical Regulator of FLT3 In Acute Myeloid Leukemia
Transcriptomics Dataset
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General Information
AccessionGSE54065
TitleSYK Is a Critical Regulator of FLT3 In Acute Myeloid Leukemia
DescriptionCooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54065
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Cell Type
Geneset
Small molecules which mimic SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse SYK knockdown
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in SYK knockdown
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in SYK knockdown
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in SYK knockdown
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in SYK knockdown
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
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