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Series GSE199373 Query DataSets for GSE199373
Status Public on Sep 21, 2023
Title Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary This SuperSeries is composed of the SubSeries listed below.

The translocation t(11;14) occurs in 20% of multiple myeloma (MM) patients and results in the upregulation of CCND1. Nearly two-thirds of t(11;14) MM cells are BCL2 primed and highly responsive to the oral BCL2 inhibitor venetoclax. While it is evident that this unique sensitivity to venetoclax depends on the BH3-proapoptotic protein priming of BCL2, the biology underlying t(11;14) MM dependency on BCL2 is poorly defined. Importantly, the epigenetic regulation of t(11;14) transcriptomes and its impact on gene regulation and clinical response to venetoclax remains elusive. In this study, by integrating ATACseq and RNAseq at the single-cell level in primary MM samples, we have defined the epigenetic regulome and transcriptome associated with t(11;14) MM. A "B cell-like" epigenetic signature was enriched in t(11;14) MM, confirming its phylogeny link to B cell rather than plasma cell biology. Of note, a loss of a "B cell-like" epigenetic signature with a gain of canonical plasma cell transcription factors was observed at the time of resistance to venetoclax. In addition, MCL1 and BCL2L1 copy number gains and structural rearrangements were linked to venetoclax resistance in t(11;14) MM patients. To date, this is the first study in which both scATAC-seq and scRNA-seq analysis are integrated into primary MM cells to obtain a deeper resolution of the epigenetic regulome and transcriptome associated with t(11;14) MM biology and venetoclax resistance.
 
Overall design Experiments were conducted on primary patient samples provided by the Tom Baker Cancer Center, after informed consent, in accordance with the Declaration of Helsinki and following the approval by the Medical Center Institutional Review Board. Unbiased mRNA and DNA profiling were conducted by using scRNA-seq, single cell ATAC-seq and sc-CNV-seq from the GemCode system (10x Genomics) accordingly to the manufacturer’s protocols.
 
Citation(s) 37729611
Submission date Mar 24, 2022
Last update date Dec 01, 2023
Contact name Nizar Bahlis
E-mail(s) nbahlis@ucalgary.ca
Phone 403-220-2801
Organization name University of Calgary
Department Divisions of Hematology and Oncology
Street address 3330 Hospital Dr NW HMRB328
City Calgary
State/province Alberta
ZIP/Postal code T2N4N1
Country Canada
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (58)
GSM5968478 Patient_1698_Post_Treatment ATAC-seq
GSM5968479 Patient_1555_Post_Treatment ATAC-seq
GSM5968480 Patient_1498_Pre_Treatment ATAC-seq
This SuperSeries is composed of the following SubSeries:
GSE199268 scATACseq Datasets Supporting Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
GSE199359 scRNAseq Datasets Supporting Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
GSE199372 scCNVseq Datasets Supporting Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
Relations
BioProject PRJNA819469

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
GSE199373_RAW.tar 8.6 Gb (http)(custom) TAR (of BED, H5)
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