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Series GSE100672

Query DataSets for GSE100672

Status

Public on Jan 26, 2019

Title

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL

Organism

Experiment type

Genome binding/occupancy profiling by high throughput sequencing

Summary

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration. By applying our method to a cohort of matched patient samples collected before and during ibrutinib therapy, we identified characteristic ibrutinib-induced changes that provide a starting point for the rational design of ibrutinib combination therapies. Specifically, we observed and validated preferential sensitivity to proteasome, PLK1, and mTOR inhibitors during ibrutinib treatment. More generally, our study establishes a broadly applicable method for investigating treatment-specific vulnerabilities by integrating the complementary perspectives of epigenetic cell states and phenotypic drug responses in primary patient samples.

Overall design

38 ATAC-seq samples from primary peripheral blood mononucleated cells (PBMC) from chronic lymphocytic leukemia patient with high leukemic cell count were produced.

Contributor(s)

Schmidl C, Vladimer GI, Rendeiro AF, Schnabl S, Pemovska T, Krausgruber T, Araghi M, Krall N, Snijder B, Hubman R, Ringler A, Demirtas D, Lopez de la Fuente O, Hilgarth M, Skrabs C, Porpaczy E, Gruber M, Hörmann G, Kubicek S, Staber PB, Shehata M, Jäger U, Superti-Furga G, Bock C

Citation(s)

Submission date

Jun 29, 2017

Last update date

Jul 25, 2021

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)

Illumina HiSeq 4000 (Homo sapiens)

Samples (38)

More...

GSM2690984	ATAC-seq for patient CLL1 during Ibrutinib treatment
GSM2690985	ATAC-seq for patient CLL1 before Ibrutinib treatment
GSM2690986	ATAC-seq for patient CLL10 before Ibrutinib treatment

GSM2690987	ATAC-seq for patient CLL10 during Ibrutinib treatment
GSM2690988	ATAC-seq for patient CLL11 before Ibrutinib treatment
GSM2690989	ATAC-seq for patient CLL11 during Ibrutinib treatment
GSM2690990	ATAC-seq for patient CLL12 before Ibrutinib treatment
GSM2690991	ATAC-seq for patient CLL12 during Ibrutinib treatment
GSM2690992	ATAC-seq for patient CLL13 before Ibrutinib treatment
GSM2690993	ATAC-seq for patient CLL13 during Ibrutinib treatment
GSM2690994	ATAC-seq for patient CLL14 before Ibrutinib treatment
GSM2690995	ATAC-seq for patient CLL14 during Ibrutinib treatment
GSM2690996	ATAC-seq for patient CLL15 before Ibrutinib treatment
GSM2690997	ATAC-seq for patient CLL15 during Ibrutinib treatment
GSM2690998	ATAC-seq for patient CLL16 before Ibrutinib treatment
GSM2690999	ATAC-seq for patient CLL16 during Ibrutinib treatment
GSM2691000	ATAC-seq for patient CLL17 before Ibrutinib treatment
GSM2691001	ATAC-seq for patient CLL17 during Ibrutinib treatment
GSM2691002	ATAC-seq for patient CLL19 before Ibrutinib treatment
GSM2691003	ATAC-seq for patient CLL19 during Ibrutinib treatment
GSM2691004	ATAC-seq for patient CLL2 during Ibrutinib treatment
GSM2691005	ATAC-seq for patient CLL2 before Ibrutinib treatment
GSM2691006	ATAC-seq for patient CLL20 before Ibrutinib treatment
GSM2691007	ATAC-seq for patient CLL20 during Ibrutinib treatment
GSM2691008	ATAC-seq for patient CLL21 during Ibrutinib treatment
GSM2691009	ATAC-seq for patient CLL21 before Ibrutinib treatment
GSM2691010	ATAC-seq for patient CLL3 before Ibrutinib treatment
GSM2691011	ATAC-seq for patient CLL3 during Ibrutinib treatment
GSM2691012	ATAC-seq for patient CLL4 before Ibrutinib treatment
GSM2691013	ATAC-seq for patient CLL4 during Ibrutinib treatment
GSM2691014	ATAC-seq for patient CLL5 during Ibrutinib treatment
GSM2691015	ATAC-seq for patient CLL5 before Ibrutinib treatment
GSM2691016	ATAC-seq for patient CLL6 before Ibrutinib treatment
GSM2691017	ATAC-seq for patient CLL6 during Ibrutinib treatment
GSM2691018	ATAC-seq for patient CLL7 before Ibrutinib treatment
GSM2691019	ATAC-seq for patient CLL7 during Ibrutinib treatment
GSM2691020	ATAC-seq for patient CLL9 before Ibrutinib treatment
GSM2691021	ATAC-seq for patient CLL9 during Ibrutinib treatment

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE100672_RAW.tar	6.2 Gb	(http)(custom)	TAR (of BIGWIG, NARROWPEAK)
GSE100672_cll-ibrutinib.coverage.csv.gz	5.5 Mb	(ftp)(http)	CSV
GSE100672_cll-ibrutinib.coverage.normalized.annotated.csv.gz	29.4 Mb	(ftp)(http)	CSV
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Raw data are available in SRA
Processed data provided as supplementary file

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