Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.
Pubmed ID: 31543463 RIS Download
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A software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)
View all literature mentionsOpen source database of curated, non-redundant set of profiles derived from published collections of experimentally defined transcription factor binding sites for multicellular eukaryotes. Consists of open data access, non-redundancy and quality. JASPAR CORE is smaller set that is non-redundant and curated. Collection of transcription factor DNA-binding preferences, modeled as matrices. These can be converted into Position Weight Matrices (PWMs or PSSMs), used for scanning genomic sequences. Web interface for browsing, searching and subset selection, online sequence analysis utility and suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. New functions include clustering of matrix models by similarity, generation of random matrices by sampling from selected sets of existing models and a language-independent Web Service applications programming interface for matrix retrieval.
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsMass spectrometry Interactive Virtual Environment (MassIVE) is a community resource developed by the NIH-funded Center for Computational Mass Spectrometry to promote the global, free exchange of mass spectrometry data. Data repository for proteomics data.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsAlignment analysis software tool for comparative mapping between two genome assemblies or between two different genomes. It can cache intermediate results to speed a comparisons of multiple sequences.
View all literature mentionsPython based tools to process, visualize and analyse high-throughput sequencing data, such as ChIP-seq, RNA-seq or MNase-seq. Implemented within Galaxy framework. Used to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches.
View all literature mentionsSoftware R package for sequence alignment and counting for R. Used for analyses of second and third generation sequencing data, for read mapping, read counting, SNP calling, short and long read alignment, quantification and mutation discovery. Includes assessment of sequence reads, read alignment, read summarization, exon-exon junction detection, fusion detection, detection of short and long indels, absolute expression calling and SNP calling. Can be used with reads generated from any of the major sequencing platforms including Illumina GA/HiSeq/MiSeq, Roche GS-FLX, ABI SOLiD and LifeTech Ion PGM/Proton sequencers.
View all literature mentionsThis monoclonal targets Human PMAIP1
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View all literature mentionsThis polyclonal targets AMPK-alpha
View all literature mentionsThis unknown targets IkappaB-alpha
View all literature mentionsThis monoclonal targets AMPK alpha
View all literature mentionsThis unknown targets Bim
View all literature mentionsThis monoclonal targets Bcl-xL (H-5)
View all literature mentionsThis monoclonal targets Human MCL1
View all literature mentionsThis monoclonal targets ID3
View all literature mentionsThis monoclonal targets UBR5
View all literature mentionsCell line SU-DHL-6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line OCI-Ly1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Toledo is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SU-DHL-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line Toledo is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SU-DHL-6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SU-DHL-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line OCI-Ly1 is a Cancer cell line with a species of origin Homo sapiens (Human)
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