TYK2 is a key regulator of the surveillance of B lymphoid tumors

Dagmar Stoiber, Boris Kovacic, Christian Schuster, Carola Schellack, Marina Karaghiosoff, Rita Kreibich, Eva Weisz, Michaela Artwohl, Olaf C Kleine, Mathias Muller, Sabina Baumgartner-Parzer, Jacques Ghysdael, Michael Freissmuth, Veronika Sexl

Research output: Journal article (peer-reviewed)Journal article

62 Citations (Scopus)


Aberrant activation of the JAK-STAT pathway has been implicated in tumor formation; for example, constitutive activation of JAK2 kinase or the enforced expression of STAT5 induces leukemia in mice. We show here that the Janus kinase TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson-induced B lymphoid leukemia/lymphoma as well as TEL-JAK2-induced T lymphoid leukemia with a higher incidence and shortened latency compared with WT controls. The cell-autonomous properties of Abelson murine leukemia virus-transformed (A-MuLV-transformed) TYK2(-/-) cells were unaltered, but the high susceptibility of TYK2(-/-) mice resulted from an impaired tumor surveillance, and accordingly, TYK2(-/-) A-MuLV-induced lymphomas were easily rejected after transplantation into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a decreased in vitro cytotoxic capacity of TYK2(-/-) NK and NKT cells toward tumor-derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV-induced leukemia/lymphoma faster than RAG2(-/-)TYK2(+/-) mice. This defines NK cells as key players in tumor surveillance in Abelson-induced malignancies. Our observations provide compelling evidence that TYK2 is an important regulator of lymphoid tumor surveillance.

Original languageEnglish
Pages (from-to)1650-1658
Number of pages9
JournalJournal of Clinical Investigation
Issue number11
Publication statusPublished - Dec 2004
Externally publishedYes


  • Abelson murine leukemia virus/genetics
  • Animals
  • Animals, Newborn
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins/genetics
  • Humans
  • Leukemia, B-Cell/immunology
  • Leukemia, Experimental/immunology
  • Leukemia, T-Cell/immunology
  • Liver/cytology
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • Neoplasm Transplantation
  • Nuclear Proteins
  • Protein-Tyrosine Kinases/genetics
  • Spleen/cytology
  • Survival Rate
  • TYK2 Kinase


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