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Series GSE111015 Query DataSets for GSE111015
Status Public on Feb 22, 2019
Title Chromatin mapping and single-cell immune profiling defines the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Chronic lymphocytic leukemia (CLL) is a genetically, epigenetically, and clinically heterogeneous disease. Despite this heterogeneity, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for the vast majority of CLL patients. To define the underlining regulatory program, we analyzed high-resolution time courses of ibrutinib treatment in closely monitored patients, combining cellular phenotyping (flow cytometry), single-cell transcriptome profiling (scRNA-seq), and chromatin mapping (ATAC-seq). We identified a consistent regulatory program shared across all patients, which was further validated by an independent CLL cohort. In CLL cells, this program starts with a sharp decrease of NF-κB binding, followed by reduced regulatory activity of lineage-defining transcription factors (including PAX5 and IRF4) and erosion of CLL cell identity, finally leading to the acquisition of a quiescence-like gene signature which was shared across several immune cell types. Nevertheless, we observed patient-to-patient variation in the speed of its execution, which we exploited to predict patient-specific dynamics in the response to ibrutinib based on pre-treatment samples. In aggregate, our study describes the cellular, molecular, and regulatory effects of therapeutic B cell receptor inhibition in CLL at high temporal resolution, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring.

This SuperSeries is composed of the SubSeries listed below.
 
Overall design 176 ATAC-seq samples of primary immune cell types from chronic lymphocytic leukemia patients and normal donors
12 scRNA-seq samples of peripheral blood mononuclear cells from chronic lymphocytic leukemia patients

Refer to individual Series for more details.
 
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Submission date Feb 22, 2018
Last update date Apr 01, 2019
Contact name Christoph Bock
E-mail(s) cbock@cemm.oeaw.ac.at
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (188)
GSM3020217 ATAC-seq on PBMCs from donor ND-1, Bcell
GSM3020218 ATAC-seq on PBMCs from donor ND-2, Bcell
GSM3020219 ATAC-seq on PBMCs from donor ND-3, Bcell
This SuperSeries is composed of the following SubSeries:
GSE111013 Chromatin mapping and single-cell immune profiling defines the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia [ATAC-seq]
GSE111014 Chromatin mapping and single-cell immune profiling defines the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia [scRNA-seq]
Relations
BioProject PRJNA435588

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE111015_RAW.tar 19.6 Gb (http)(custom) TAR (of BIGWIG, NARROWPEAK)

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