Gene expression changes associated with progression and response in chronic myeloid leukemia
Transcriptomics Dataset
FAIR Metrics
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General Information
AccessionGSE4170
TitleGene expression changes associated with progression and response in chronic myeloid leukemia
DescriptionChronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. The biological foundation of the stereotypical progression from chronic phase through accelerated phase to blast crisis is poorly understood. We used DNA microarrays to compare gene expression in 91 cases of CML in chronic (42 cases), accelerated (17 cases), and blast phases (32 cases). Three thousand genes were found to be significantly (p<10-10) associated with the progression from chronic to blast phase. A comparison of the gene signatures of chronic, accelerated, and blast phases suggest that the progression of chronic phase CML from chronic advanced phase (accelerated and blast crisis) CML is a two-step rather than a three-step process, with new gene expression changes occurring early in accelerated phase before the accumulation of increased leukemia blast cells. The genetic signature of advanced phase CML is similar to that of normal CD34+ cells; however, progression also involved novel genes not expressed in normal CD34+ cells. Especially noteworthy is deregulation of the WNT/b-catenin pathway, the decreased expression of both JunB and Fos, and dysregulation of genes under the control of MZF1 and delta EF1 zinc finger transcription factors. Studies of CML patients who relapsed after initially successful treatment with imatinib mesylate demonstrated a gene expression pattern closely related to advanced phase disease. Take together, these data suggest that CML progression begins relative early and before clinical and pathological detection, and features distinct genetic differences compared to normal hematpoetic cells that might provide diagnostic and therapeutic targets. Keywords: disease state analysis
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4170
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
Geneset
Interaction network and enrichment analysis of genes downregulated in chronic myeloid leukemia
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in chronic myeloid leukemia
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Small molecules which mimic chronic myeloid leukemia
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse chronic myeloid leukemia
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in chronic myeloid leukemia
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes downregulated in chronic myeloid leukemia
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in chronic myeloid leukemia
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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