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Open Access

PI3Kδ: a double-edged sword in leukemia formation

  • Eva-Maria Zebedin1,
  • Olivia Simma1,
  • Christian Schuster1,
  • Eva Eckelhart1,
  • Wolgang Warsch1,
  • Dagmar Stoiber2,
  • Eva Weisz2,
  • Winfried F Pickl3,
  • Roland Piekorz4,
  • Michael Freissmuth1 and
  • Veronika Sexl1Email author
BMC Pharmacology20077(Suppl 2):A7

https://doi.org/10.1186/1471-2210-7-S2-A7

Published: 14 November 2007

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. Abelson-transformed 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.

Authors’ Affiliations

(1)
Department of Pharmacology, Medical University of Vienna
(2)
Ludwig Boltzmann Institute for Cancer Research
(3)
Department of Immunology, Medical University of Vienna
(4)
Institute of Biochemistry and Molecular Biology II, Heinrich-Heine-University Düsseldorf

Copyright

© Zebedin et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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