Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
TYK2 is a key regulator of the surveillance of B lymphoid tumors
Dagmar Stoiber, … , Michael Freissmuth, Veronika Sexl
Dagmar Stoiber, … , Michael Freissmuth, Veronika Sexl
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1650-1658. https://doi.org/10.1172/JCI22315.
View: Text | PDF
Article Oncology

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

  • Text
  • PDF
Abstract

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.

Authors

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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Effect of in vivo oncogenic challenge with the Abelson oncogene. (A) Kap...
Effect of in vivo oncogenic challenge with the Abelson oncogene. (A) Kaplan-Meier plot of TYK2+/– and TYK2–/– mice after injection of a replication-incompetent A-MuLV retrovirus (n = 20 for each group). All 20 TYK2–/– mice died of leukemia/lymphoma within 10 weeks, whereas 6 TYK2+/– mice remained disease free for more than 6 months. (B) White blood cell count of the diseased TYK2+/– and TYK2–/– animals (n = 8 for TYK2–/– and n = 15 for TYK2+/–). (C) H&E-stained blood smears of TYK2+/– and TYK2–/– mice (magnification, ×200). Typical examples of each genotype are shown. (D) H&E-stained histological sections (magnification, ×200) of liver (upper panels) and spleen (lower panels) of TYK2+/– and TYK2–/– animals. One representative example is depicted.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts