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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Short Communication

Jahr: 2017

AutorInnen: Boidol, B; Kornauth, C; van der Kouwe, E; Prutsch, N; Kazianka, L; Gültekin, S; Hoermann, G; Mayerhoefer, ME; Hopfinger, G; Hauswirth, A; Panny, M; Aretin, MB; Hilgarth, B; Sperr, WR; Valent, P; Simonitsch-Klupp, I; Moriggl, R; Merkel, O; Kenner, L; Jäger, U; Kubicek, S; Staber, PB

Titel: First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.

Quelle: Blood. 2017; 130(23):2499-2503



Autor/innen der Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Funktionelle Krebsgenomik


Abstract:
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia 1 (MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL.© 2017 by The American Society of Hematology.

Keywords Pubmed: Adult
Antineoplastic Agentspharmacologytherapeutic use
Antineoplastic Combined Chemotherapy Protocolsadverse effectstherapeutic use
Bridged Bicyclo Compounds, Heterocyclicpharmacologytherapeutic use
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Evaluation, Preclinicalmethods
Drug Resistance, Neoplasm
Female
High-Throughput Screening Assays
Humans
Leukemia, Prolymphocytic, T-Celldiagnosisdrug therapymetabolism
Male
Middle Aged
Molecular Targeted Therapy
Proto-Oncogene Proteins c-bcl-2antagonists & inhibitors
Recurrence
Sulfonamidespharmacologytherapeutic use
Treatment Outcome

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