2020
DOI: 10.1002/1878-0261.12753
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Identification of BLNK and BTK as mediators of rituximab‐induced programmed cell death by CRISPR screens in GCB‐subtype diffuse large B‐cell lymphoma

Abstract: Diffuse large B‐cell lymphoma (DLBCL) is characterized by extensive genetic heterogeneity, and this results in unpredictable responses to the current treatment, R‐CHOP, which consists of a cancer drug combination supplemented with the humanized CD20‐targeting monoclonal antibody rituximab. Despite improvements in the patient response rate through rituximab addition to the treatment plan, up to 40% of DLBCL patients end in a relapsed or refractory state due to inherent or acquired resistance to the regimen. Her… Show more

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Cited by 19 publications
(24 citation statements)
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“…Stable integration of gene cassettes encoding conventional CRISPR effectors, like Cas9 and single guide RNAs, into the genome of mammalian cells is widely used across life science research, including for generation of model cell lines and in CRISPR screens ( Shalem et al, 2014 ; Holmgaard et al, 2017 ; Thomsen et al, 2020 ). For prime editing, effective integration of the PE2-expressing cassette into the genome of mammalian cells is challenged by the large size of the PE2 coding sequence (6351 bp).…”
Section: Introductionmentioning
confidence: 99%
“…Stable integration of gene cassettes encoding conventional CRISPR effectors, like Cas9 and single guide RNAs, into the genome of mammalian cells is widely used across life science research, including for generation of model cell lines and in CRISPR screens ( Shalem et al, 2014 ; Holmgaard et al, 2017 ; Thomsen et al, 2020 ). For prime editing, effective integration of the PE2-expressing cassette into the genome of mammalian cells is challenged by the large size of the PE2 coding sequence (6351 bp).…”
Section: Introductionmentioning
confidence: 99%
“…We found that ErbB2 promotes survival of breast cancer cell detached from the ECM by a novel mechanism involving downregulation of transcription factor IRF6 and further downregulation of the cell death-promoting protein BLNK [ 23 , 35 ]. ErbB2-induced BLNK downregulation likely blocks the apoptotic form of death of detached cancer cells since we observed that ectopic BLNK triggers apoptosis symptoms in the cells, such as caspase-3 cleavage and Annexin V positivity (Fig.…”
Section: Discussionmentioning
confidence: 99%
“… 31 pPBT/EFS-Cas9-PuroTK was cloned by insertion of a PCR-amplified PuroTK fragment from pCCL/pBT.PuroTK-CMV (unpublished data) into BamHI- and NdeI-digested pPBT/EFS-Cas9-Blast (unpublished data) using NEBuilder HIFI DNA Assembly (New England Biolabs, Ipswich, MA, USA). pLV/Guide-mCherry was cloned by digesting pLV/Guide-Puro 41 with BsiWI and Mlul and amplifying mCherry from pT2/CMV-SerpinG1-linker-mCherry. Similarly, plenti/Cas9-mCherry was cloned by digesting plentiCas9-Blast 42 with BamHI and EcoRI and inserting the mCherry sequence amplified from pLV/Guide-mCherry by a nested extension PCR to include P2A between Cas9 and mCherry.…”
Section: Methodsmentioning
confidence: 99%