Title of article
Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma
Author/Authors
Yang، نويسنده , , Yibin and Shaffer III، نويسنده , , Arthur L. and Emre، نويسنده , , N.C. Tolga and Ceribelli، نويسنده , , Michele and Zhang، نويسنده , , Meili and Wright، نويسنده , , George and Xiao، نويسنده , , Wenming and Powell، نويسنده , , John and Platig، نويسنده , , John and Kohlhammer، نويسنده , , Holger and Young، نويسنده , , Ryan M. and Zhao، نويسنده , , Hong and Yang، نويسنده , , Yandan and Xu، نويسنده , , Weihong and Buggy، نويسنده , , Joseph J. and Balasubramanian، نويسنده , , Sriram and Mathews، نويسنده , , Lesley A. and Shinn، نويسنده , , Paul and Guha، نويسنده , , Rajarshi and Ferrer، نويسنده , , Marc and Thomas، نويسنده , , Craig and Waldmann، نويسنده , , Thomas A. and Staudt، نويسنده , , Louis M.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2012
Pages
15
From page
723
To page
737
Abstract
Summary
dge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), but its mechanism of action is unknown. Lenalidomide kills ABC DLBCL cells by augmenting interferon β (IFNβ) production, owing to the oncogenic MYD88 mutations in these lymphomas. In a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNβ production by repressing IRF7 and amplify prosurvival NF-κB signaling by transactivating CARD11. Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.
Journal title
Cancer Cell
Serial Year
2012
Journal title
Cancer Cell
Record number
1337914
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