RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates Fasudil as an anti-leukemic drug.
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
AccessionGSE68925
TitleRNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates Fasudil as an anti-leukemic drug.
DescriptionAcute myeloid leukemia (AML) is characterized by a marked genetic heterogeneity, which complicates the development of novel therapeutics. The delineation of pathways essential within the patient-individual mutational background might overcome this limitation and facilitate personalized treatment. We report the results of a large-scale lentiviral loss-offunction RNA-interference-(RNAi)-screen in primary leukemic cells. Stringent validation identified six genes (BNIPL1, ROCK1, RPS13, STK3, SNX27, WDHD1) whose knockdown impaired growth and viability of the cells. Dependence on these genes was not caused by mutation or overexpression and while some of the candidates seemed to be rather patientspecific, others were essential in cells isolated from other AML patients. In addition to the phenotype observed after ROCK1 knockdown, treatment with the approved ROCK-inhibitor fasudil resulted in increased apoptosis and decreased viability of primary AML cells. In contrast to observations in some other malignancies, ROCK1-inhibition did not foster growth of immature malignant progenitors; but was also toxic to this cell fraction in feeder-co-culture and xenotransplantion experiments, indicating a distinct effect of ROCK1 inhibition on leukemic progenitors. We conclude that large scale RNAi screens in primary patient-derived cells are feasible and can complement other methods for personalized cancer therapies, such as expression and mutation profiling.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68925
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Interactive heatmap visualization of RNA-seq dataset GSE68925
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.