GSE111015 Chromatin mapping and single-cell immune profiling defines the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia

Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Homo sapiensChronic lymphocytic leukemia (CLL) is a genetically, epigenetically, and clinically heterogeneous disease. Despite this heterogeneity, the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib induces a sustained anti-CLL response in patients from all risk groups, in stark contrast to widespread drug resistance in other heterogeneous cancers. To understand the dynamics of ibrutinib response against the backdrop of patient-specific and heterogeneous disease manifestations, we followed individual courses of ibrutinib treatment in CLL patients at unprecedented resolution and detail. Combining phenotypic (flow cytometry), epigenetic (ATAC-seq), and transcriptional (single-cell RNA-seq) profiling of CLL cells and other immune cell populations with detailed clinical characterization, we inferred patient-specific molecular trajectories of treatment response. This analysis identified a highly consistent regulatory program shared across all patients, which starts with reduced NF- κB binding followed by reduced expression of lineage defining transcription factors, erosion of CLL cell identity, and onset of a gene signature reminiscent of quiescence in several immune cell compartments. While this order of events was highly conserved across patients, and its gene signature was validated in an independent CLL cohort, we observed substantial...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Homo sapiens Source Type: research