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Series GSE225263 Query DataSets for GSE225263
Status Public on Apr 10, 2024
Title Functional investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment [MPRA]
Organisms Homo sapiens; synthetic construct
Experiment type Other
Summary Although acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, there is limited understanding of the contribution of inherited genetic variation on inter-individual differences in chemotherapy response, and defining genetic factors impacting therapy failure can help better predict response and identify drug resistance mechanisms. Using inherited noncoding variants associated with chemotherapeutic drug resistance and/or treatment outcome, we mapped these variants to ALL cis-regulatory elements and investigated their gene regulatory potential and genomic connectivity using massively parallel reporter assays and promoter capture Hi-C, respectively. We identified 53 variants with reproducible allele-specific effects on transcription and high-confidence gene targets. Subsequent functional interrogation of the top variant (rs1247117) determined that it disrupted a PU.1 consensus motif and PU.1 binding affinity. Importantly, deletion of the genomic interval containing rs1247117 sensitized ALL cells to vincristine. Together, these data demonstrate that noncoding regulatory variation associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to chemotherapeutic agents in ALL.
Overall design MPRA in 10 ALL cell lines
Contributor(s) Raj Bhattarai K, Mobley RJ, Barnett KR, Ferguson DC, Diedrich JD, Bergeron BP, Yang W, Crews KR, Jabbour E, Manring CS, Paietta E, Kornblau SM, Stock W, Inaba H, Jeha S, Pui C, Cheng C, Relling MV, Evans WE, Yang JJ, Savic D
Citation(s) 38693155
Submission date Feb 14, 2023
Last update date May 24, 2024
Contact name Daniel Savic
Organization name St. Jude Children's Research Hospital
Department Pharmaceutical Sciences
Lab Savic
Street address 262 Danny Thomas pl.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
Platforms (2)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
GPL26526 Illumina NovaSeq 6000 (synthetic construct)
Samples (64)
GSM7042908 JurkatMPRA001
GSM7042909 JurkatMPRA002
GSM7042910 JurkatMPRA003
This SubSeries is part of SuperSeries:
GSE224204 Functional investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
BioProject PRJNA934850

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
GSE225263_697_MPRA_Counts_AggregateSums.tsv.gz 42.5 Kb (ftp)(http) TSV
GSE225263_BALL1_MPRA_Counts_AggregateSums.tsv.gz 36.7 Kb (ftp)(http) TSV
GSE225263_CEM_MPRA_Counts_AggregateSums.tsv.gz 43.2 Kb (ftp)(http) TSV
GSE225263_DNAInputPDX_MPRA_Counts_AggregateSums.tsv.gz 45.7 Kb (ftp)(http) TSV
GSE225263_DNAInput_MPRA_Counts_AggregateSums.tsv.gz 42.9 Kb (ftp)(http) TSV
GSE225263_Jurkat_MPRA_Counts_AggregateSums.tsv.gz 42.4 Kb (ftp)(http) TSV
GSE225263_MPRA_ALL_CELL_LINES.txt.gz 773.6 Kb (ftp)(http) TXT
GSE225263_Nalm6_MPRA_Counts_AggregateSums.tsv.gz 44.1 Kb (ftp)(http) TSV
GSE225263_P12-Ichikawa_MPRA_Counts_AggregateSums.tsv.gz 43.7 Kb (ftp)(http) TSV
GSE225263_PDX1137_MPRA_Counts_AggregateSums.tsv.gz 39.6 Kb (ftp)(http) TSV
GSE225263_PDX4420_MPRA_Counts_AggregateSums.tsv.gz 43.9 Kb (ftp)(http) TSV
GSE225263_REH_MPRA_Counts_AggregateSums.tsv.gz 36.7 Kb (ftp)(http) TSV
GSE225263_RS411_MPRA_Counts_AggregateSums.tsv.gz 40.2 Kb (ftp)(http) TSV
GSE225263_SEM_MPRA_Counts_AggregateSums.tsv.gz 36.3 Kb (ftp)(http) TSV
GSE225263_SUPB15_MPRA_Counts_AggregateSums.tsv.gz 39.8 Kb (ftp)(http) TSV
GSE225263_barcodes.txt.gz 1007.2 Kb (ftp)(http) TXT
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