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Series GSE256495 Query DataSets for GSE256495
Status Public on Apr 17, 2024
Title Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy.
 
Overall design Bulk ATAC sequencing of bulk AML cells, AML blasts, and AML LSCs at diagnosis and relapse post-chemotherapy. Single cell ATAC sequencing of diagnosis and relapse bulk AML cells.
 
Contributor(s) Nuno KA, Azizi A, Köhnke T, Lareau CA, Ediwirickrema A, Corces MR, Satpathy AT, Majeti R
Citation(s) 38647535
Submission date Feb 23, 2024
Last update date May 10, 2024
Contact name Ravindra Majeti
E-mail(s) rmajeti@stanford.edu
Organization name Stanford University
Lab Ravindra Majeti
Street address 875 Blake Wilbur Dr Clinic F
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (195)
GSM8101643 Patient SU042 Diagnosis timepoint Blast replicate 1 ATACseq Sample
GSM8101644 Patient SU042 Diagnosis timepoint Blast replicate 2 ATACseq Sample
GSM8101645 Patient SU042 Relapse timepoint Blast replicate 1 ATACseq Sample
Relations
BioProject PRJNA1079789

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Supplementary file Size Download File type/resource
GSE256495_bulk_count_matrix_raw.rds.gz 34.1 Mb (ftp)(http) RDS
GSE256495_bulk_gene_scores.rds.gz 33.2 Mb (ftp)(http) RDS
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