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Homo sapiens

ABSTRACT: Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

PROVIDER: PRJNA321180 | ENA |

REPOSITORIES: ENA

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Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

Project description:Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status â which distinguishes the two major subtypes of CLL â was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research. Genome-wide profiling of chromatin states and gene expression levels in 88 CLL samples from 55 individuals gave rise to 88 ATAC-seq profiles, 40 ChIPmentation profiles (10 samples, each with 3 different antibodies and matched immunoglobulin control), and 10 RNA-seq profiles. Raw sequence data has been deposited at the EBI's European Genome-phenome Archive (EGA) under the accession number EGAS00001001821 (controlled access to protect patient privacy).

2016-06-26 | E-GEOD-81274 | biostudies-arrayexpress

Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

Project description:Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.

2016-06-26 | GSE81274 | GEO

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Rodrigues2019 - A mathematical model for chemoimmunotherapy of chronic lymphocytic leukemia

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Treatment of MEC1, EHEB and JVM2 leukemia cell lines with fludarabine, ibrutinib and idelalisib

Project description:UGT2B17 is a recently identified molecular marker for poor prognosis and drug response in Chronic Lymphocytic Leukemia (CLL), which is the most prevalent adult leukemia subtype in the western world. The goal of this study was to investigate transcriptome changes associated with drug-induced UGT2B17 up-regulation to identify possible upstream regulators of drug response and downstream effects of UGT induction.

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Nanda2013 - B cell chronic lymphocytic leukemia A model with immune response

Project description:B cell chronic lymphocytic leukemia - A model with immune response Seema Nanda 1, , Lisette dePillis 2, and Ami Radunskaya 3, 1. Tata Institute of Fundamental Research, Centre for Applicable Mathematics, Bangalore 560065, India 2. Department of Mathematics, Harvey Mudd College, Claremont, CA 91711 3. Department of Mathematics, Pomona College, Claremont, CA, 91711, United States Abstract B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet flexible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based. Keywords: NK cell, chronic lymphocytic leukemia, mathematical model, T cell., B-CLL.

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