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Status |
Public on Feb 28, 2022 |
Title |
Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse [RRBS] |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDXs), we identify the polycomb repressive complex 2 (PRC2) as key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacological inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells.
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Overall design |
Analysis of methylation profile of primary and 3 post transplantation from PDXs relapse compared to their controls at diagnosis.
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Contributor(s) |
Gambacorta V, Beretta S, Cittaro D, Merelli I, Di Micco R, Vago L |
Citation(s) |
35255120 |
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Submission date |
Feb 24, 2022 |
Last update date |
May 30, 2022 |
Contact name |
Stefano Beretta |
E-mail(s) |
beretta.stefano1@hsr.it
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Organization name |
San Raffaele Telethon Institute for Gene Therapy
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Street address |
Via Olgettina, 60
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City |
Milan |
ZIP/Postal code |
20132 |
Country |
Italy |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (8)
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GSM5917153 |
RRBS_AML patient UPN01 at diagnosis |
GSM5917154 |
RRBS_AML patient UPN01 at relapse (post transpantation) |
GSM5917155 |
RRBS_Patient Derived Xenografts UPN01 at diagnosis, rep 1 |
GSM5917156 |
RRBS_Patient Derived Xenografts UPN01 at relapse, rep 1 |
GSM5917157 |
RRBS_Patient Derived Xenografts UPN01 at diagnosis, rep 2 |
GSM5917158 |
RRBS_Patient Derived Xenografts UPN01 at relapse, rep 2 |
GSM5917159 |
RRBS_Patient Derived Xenografts UPN01 at diagnosis, rep 3 |
GSM5917160 |
RRBS_Patient Derived Xenografts UPN01 at relapse, rep 3 |
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This SubSeries is part of SuperSeries: |
GSE197419 |
Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse |
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Relations |
BioProject |
PRJNA810180 |