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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Temsirolimus inhibits cell growth in combination with inhibitors of the B-cell receptor pathway.
Leuk. Lymphoma 56, 3393-3400 (2015)
Lately, mTOR inhibitors have gained clinical relevance in malignant lymphoma. Still, rapamycin derivatives may activate a pro-survival feedback loop through PI3K-Akt. In this current study, temsirolimus effectively reduced cell growth in GCB and ABC diffuse large cell B-cell lymphoma (GCB = 30–66%, ABC = 45–57%). Combination treatment with the PI3K-δ inhibitor idelalisib additively effected ABC and GCB lymphoma (GCB = 16–38%, ABC = 25–50%). Since Bruton's Tyrosine Kinase (BTK) plays a significant role for the survival of ABC lymphoma, this study also combined the BTK inhibitor ibrutinib with temsirolimus, which resulted in additive cell growth reduction (ibrutinib 50%, temsirolimus 44%, combination 25%) in ABC lymphoma. In contrast, bortezomib, which has been shown previously to be efficient in ABC lymphoma, revealed an antagonistic effect with temsirolimus in some GCB lymphoma (temsirolimus 53%, temsirolimus + bortezomib 63%). Western blot analysis identified the increase of phosphorylated pro-survival kinases Akt and PDK as a possible underlying mechanism of this interaction.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Dlbcl ; Mtor ; Pi3k ; Temsirolimus
ISSN (print) / ISBN
1042-8194
e-ISSN
1029-2403
Zeitschrift
Leukemia and Lymphoma
Quellenangaben
Band: 56,
Heft: 12,
Seiten: 3393-3400
Verlag
Informa Healthcare
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed