GSE118707 RNA-Seq study of Cell lines rendered resistant to idelalisib and ibrutinib

Contributors : Eva-Laure Matera ; Julien Fouret ; Estelle Baulu ; Emeline Perrial ; Zineb Bousfiha ; Lars P Jordheim ; Chettab Abdelkamel ; Joel Lachuer ; Charles dumontetSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBCR pathway inhibitors idelalisib and ibrutinib are the first small molecule targeted agents for B-cell malignancies. In spite of encouraging response rates in various forms of B cell diseases, patients will eventually develop relapse due to the emergence of resistant cells. To better identify the possible mechanisms of resistance we developed and characterized idelalisib- and ibrutinib-resistant variants of the human non Hodgkin ’s lymphoma cell lines DoHH2 and Daudi. These resistant variants displayed a cross-resistance profile limited to PI3K inhibitors, BTK inhibitors and a SYK inhibitor but not to unrelated agents. A number of alterations were observed in the resistant lines, including a strong reduction of the Akt3 p rotein. Resistant lines tended to express larger amounts of CD38 and CD52 on their cell membrane and were found to display enhanced sensitivity to anti-CD38 antibodies. These results identify potential novel mechanisms of resistance to idelalisib and ibrutinib and raise the possibility that cells re sistant to BCR pathway inhibitors might possess enhanced sensitivity to anti-CD38 antibodies.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research