Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression
Christian Schürch, … , Alexandar Tzankov, Adrian F. Ochsenbein
Christian Schürch, … , Alexandar Tzankov, Adrian F. Ochsenbein
Published January 9, 2012
Citation Information: J Clin Invest. 2012;122(2):624-638. https://doi.org/10.1172/JCI45977.
View: Text | PDF
Research Article Hematology Article has an altmetric score of 5

CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression

  • Text
  • PDF
Abstract

Chronic myelogenous leukemia (CML) results from a chromosomal translocation in hematopoietic stem or early progenitor cells that gives rise to the oncogenic BCR/ABL fusion protein. Clinically, CML has a chronic phase that eventually evolves into an accelerated stage and blast crisis. A CML-specific immune response is thought to contribute to the control of disease. Whether the immune system can also promote disease progression is not known. In the present study, we investigated the possibility that the TNF receptor family member CD27 is present on leukemia stem cells (LSCs) and mediates effects of the immune system on CML. In a mouse model of CML, BCR/ABL+ LSCs and leukemia progenitor cells were found to express CD27. Binding of CD27 by its ligand, CD70, increased expression of Wnt target genes in LSCs by enhancing nuclear localization of active β-catenin and TRAF2- and NCK-interacting kinase (TNIK). This resulted in increased proliferation and differentiation of LSCs. Blocking CD27 signaling in LSCs delayed disease progression and prolonged survival. Furthermore, CD27 was expressed on CML stem/progenitor cells in the bone marrow of CML patients, and CD27 signaling promoted growth of BCR/ABL+ human leukemia cells by activating the Wnt pathway. Since expression of CD70 is limited to activated lymphocytes and dendritic cells, our results reveal a mechanism by which adaptive immunity contributes to leukemia progression. In addition, targeting CD27 on LSCs may represent an attractive therapeutic approach to blocking the Wnt/β-catenin pathway in CML.

Authors

Christian Schürch, Carsten Riether, Matthias S. Matter, Alexandar Tzankov, Adrian F. Ochsenbein

×

Figure 9

CD27-TRAF2-TNIK signaling induces the Wnt pathway in human leukemia cells.

Options: View larger image (or click on image) Download as PowerPoint
CD27-TRAF2-TNIK signaling induces the Wnt pathway in human leukemia cell...
(A) Expression of TNIK and TRAF2 in BCR/ABL+ SD-1 cells and control T293 cells (left panel) and immunoprecipitation for TRAF2 in SD-1 cells, followed by Western blot for TRAF2 and TNIK (right panel). (B) Quantitative real-time RT-PCR of selected Wnt target genes in SD-1 cells stably expressing a scrambled shRNA (scrRNA), an shRNA against TNIK (shTNIK), or TRAF2 (shTRAF2). (C) Immunostainings for active β-catenin in SD-1 cells stably expressing scrRNA, shTNIK, or shTRAF2. Overlays of DAPI and β-catenin are shown. Scale bars: 5 μm. (D and E) Percentages of nuclear active β-catenin in SD-1 cells stably expressing (D) scrRNA versus shTNIK and (E) scrRNA versus shTRAF2. 110–226 cells were analyzed per group in 2 independent experiments. (F and G) 105 parental SD-1 cells, SD-1 cells stably expressing scrRNA, (F) shTNIK, or (G) shTRAF2 were cultured in the presence or absence of 10 μg/ml mouse control IgG or blocking anti-CD27 Ab. Numbers of viable cells were daily determined by trypan blue staining. Each condition was run in duplicate in 2 independent experiments. Data are displayed as mean ± SEM. Statistics: Student’s t test (D and E); 2-way ANOVA (F and G) (P value indicates comparison of each of the upper 4 versus each of the lower 5 conditions).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 4 X users
Referenced in 7 patents
64 readers on Mendeley
See more details