PuSH - Publikationsserver des Helmholtz Zentrums München: Important role of Caspase-8 for chemo-sensitivity of ALL cells.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Ehrhardt, H. ; Wachter, F. ; Maurer, M. ; Stahnke, K.* ; Jeremias, I.

Important role of Caspase-8 for chemo-sensitivity of ALL cells.

Clin. Cancer Res. 17, 7605-7613 (2011)

Verlagsversion

DOI

PMC

	Closed

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

Abstract
Metriken
Zusatzinfos

PURPOSE: Sensitivity of tumor cells towards chemotherapy mainly determines the prognosis of patients suffering from acute lymphoblastic leukemia (ALL); nevertheless, underlying mechanisms regulating chemo-sensitivity remain poorly understood. Here, we aimed at characterizing the role of Caspase-8 for chemo-sensitivity of B- and T-ALL cells. EXPERIMENTAL DESIGN: Primary tumor cells from children with ALL were evaluated for expression levels of the Caspase-8 protein, were amplified in NSG-mice, transfected with siRNA and evaluated for their chemo-sensitivity in vitro. RESULTS: Effective cell death in B- and T-ALL cells depended on the presence of Caspase-8 for the majority of cytotoxic drugs routinely used in anti-leukemia treatment. Caspase-8 was activated independently from extrinsic apoptosis signaling. Accordingly in primary ALL cells, the expression level of Caspase-8 protein correlated with cell death sensitivity towards defined cytotoxic drugs in vitro. In the subgroup of primary ALL cells with low expression of Caspase-8, methotrexate upregulated the expression of Caspase-8 mediated by the transcription factor p53 suggesting epigenetic silencing of Caspase-8. RNA interference in patient-derived B- and T-ALL cells revealed that effective cell death induction by most routine drug combinations involving methotrexate depended on the presence of Caspase-8. CONCLUSION: Our results indicate that Caspase-8 is crucial for the high anti-leukemic efficiency of numerous routine cytotoxic drugs. Re-expression of epigenetically downregulated Caspase-8 represents a promising approach to increase efficiency of anti-leukemic therapy.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

7.338

1.834