Abstract
The PI3Kδ isoform is a candidate drug target in leukemia. Here, we explored its role in Abelson-induced leukemia. Frank leukemia emerges if the tumor cells have managed to outwit the immune system. The absence of PI3Kδ affected both the tumor cells and the NK cells. Abelsontransformed PI3Kδ-/cells induced leukemia in RAG2-/animals with a significantly increased latency, implicating PI3Kδ in tumor progression. NK cell function, however, was also contingent on PI3Kδ. PI3Kδ-/NK cells failed to lyse target cells. Capacitance measurements revealed the underlying defect: in PI3Kδ-/NK cells lytic granules did not fuse with the cell membrane. Accordingly, transplanted leukemic cells killed PI3Kδ-/animals more rapidly, both in syngeneic (PI3Kδ-/-) or immunocompromised (RAG2-/PI3Kδ-/-) animals. Our observations define a dual function of PI3Kδ in leukemia and document that the action of PI3Kδ in the NK compartment is as relevant to the survival of the mice as the delayed tumor progression. from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT) Vienna, Austria. 22–24 November 2007
Highlights
Eva-Maria Zebedin1, Olivia Simma1, Christian Schuster1, Eva Eckelhart1, Wolgang Warsch1, Dagmar Stoiber2, Eva Weisz2, Winfried F Pickl3, Roland Piekorz4, Michael Freissmuth1 and Veronika Sexl*1
Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT) Ernst Singer and Thomas Griesbacher Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here http://www.biomedcentral.com/content/pdf/1471-2210-7-S2-info.pdf
Frank leukemia emerges if the tumor cells have managed to outwit the immune system
Summary
Eva-Maria Zebedin1, Olivia Simma1, Christian Schuster1, Eva Eckelhart1, Wolgang Warsch1, Dagmar Stoiber2, Eva Weisz2, Winfried F Pickl3, Roland Piekorz4, Michael Freissmuth1 and Veronika Sexl*1. PI3Kδ: a double-edged sword in leukemia formation Address: 1Department of Pharmacology, Medical University of Vienna, Austria, 2Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria, 3Department of Immunology, Medical University of Vienna, Austria and 4Institute of Biochemistry and Molecular Biology II, Heinrich-HeineUniversity Düsseldorf, Germany Email: Veronika Sexl* - veronika.sexl@meduniwien.ac.at * Corresponding author from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR).
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