NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE222675 Query DataSets for GSE222675
Status Public on May 01, 2024
Title Clonal evolution of the 3D chromatin landscape of relapsed ALL [ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains one of the leading causes of cancer mortality in children. Up to 20% of children will suffer relapse and face a poor prognosis. Our recent work on the evolution of the epigenetic landscape from diagnosis to relapse demonstrates both substantial diversity in the chromatin landscape as well as shared relapse-specific superenhancer activation, highlighting the importance of chromatin changes in disease progression. However, there is a gap in our understanding of B-ALL progression through the lens of three-dimensional (3D) chromosome topology. To uncover 3D chromatin architecture-related mechanisms underlying drug resistance in B-ALL, we performed Hi-C, ATAC-seq, and RNA-seq on 12 matched primary pediatric leukemia specimens at diagnosis and relapse. Mapping of structural variations (SVs) using Hi-C data revealed previously unidentified stable, diagnosis-specific, and relapse-specific SVs providing further evidence for clonal evolution as a mechanism for drug resistance. Moreover, Hi-C analysis revealed genome wide chromatin remodeling specifically in terms of A/B compartments, TAD interactivity, and chromatin loops. Integration with ATAC-seq and RNA-seq datasets revealed strong correlation with both gene expression and chromatin accessibility. Additionally, we identified recurrent A/B compartments and TAD interactivity changes across the patient cohort for which we were able to demonstrate a crucial role in the clonal evolution of B-ALL. Shared changes in 3D genome organization drive the expression of genes/pathways previously implicated in drug resistance as well. Lastly, enrichment analysis revealed key upstream regulators of 3D genome architecture in B-ALL disease progression. These results extend the landscape of genetic alterations in relapsed B-ALL through the addition of the 3D genomic landscape and identify a breadth of novel therapeutic targets.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data from 12 matched primary pediatric leukemia specimens at diagnosis and relapse.
 
Contributor(s) Narang S, Ghebrechristos Y, Evensen NA, Jasinski S, Ostrow TH, Witkowski M, Aifantis I, Tsirigos A, Carroll WL
Citation(s) 39198446
Submission date Jan 11, 2023
Last update date Sep 27, 2024
Contact name Sonali Narang
E-mail(s) sonali.narang@nyulangone.org
Phone 5169652665
Organization name NYU Langone
Street address 435 east 30th street
City New York
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (24)
GSM6928819 PATSAH-D ATAC
GSM6928820 PATSAH-R ATAC
GSM6928821 PATJJX-D ATAC
This SubSeries is part of SuperSeries:
GSE222687 Clonal evolution of the 3D chromatin landscape of relapsed ALL
Relations
BioProject PRJNA923005

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

Supplementary file Size Download File type/resource
GSE222675_RAW.tar 8.3 Gb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.