Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes

Background Anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL) shows 60–70% event free survival with standard treatments. Targeted therapies are being tested for increased benefit and/or reduced toxicity, but interactions with standard agents are not well known. Methods W...

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Veröffentlicht in:Pediatric blood & cancer 2018-08, Vol.65 (8), p.e27094-n/a
Hauptverfasser: Hudson, Sandra, Wang, Dongliang, Middleton, Frank, Nevaldine, Barbara H., Naous, Rana, Hutchison, Robert E.
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Sprache:eng
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Zusammenfassung:Background Anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL) shows 60–70% event free survival with standard treatments. Targeted therapies are being tested for increased benefit and/or reduced toxicity, but interactions with standard agents are not well known. Methods We exposed four ALCL cell lines to two targeted agents, crizotinib and brentuximab vedotin, and to two standard agents, doxorubicin and vinblastine. For each agent and combination, we measured apoptosis and expression of approximately 300 previously annotated genes of interest using targeted RNA‐sequencing. An aurora kinase inhibitor, alisertib, was similarly tested for gene expression effects. Results Only crizotinib, alone or in combination, showed significant effects (adjusted P 
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.27094