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Tetraspanin CD37 protects against the development of B cell lymphoma.

Publication ,  Journal Article
de Winde, CM; Veenbergen, S; Young, KH; Xu-Monette, ZY; Wang, X-X; Xia, Y; Jabbar, KJ; van den Brand, M; van der Schaaf, A; Elfrink, S ...
Published in: J Clin Invest
February 2016

Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that deficiency of tetraspanin superfamily member CD37, which is important for B cell function, induces the development of B cell lymphoma. Mice lacking CD37 developed germinal center-derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice. We discovered that CD37 interacts with suppressor of cytokine signaling 3 (SOCS3); therefore, absence of CD37 drives tumor development through constitutive activation of the IL-6 signaling pathway. Moreover, animals deficient for both Cd37 and Il6 were fully protected against lymphoma development, confirming the involvement of the IL-6 pathway in driving tumorigenesis. Loss of CD37 on neoplastic cells in patients with diffuse large B cell lymphoma (DLBCL) directly correlated with activation of the IL-6 signaling pathway and with worse progression-free and overall survival. Together, this study identifies CD37 as a tumor suppressor that directly protects against B cell lymphomagenesis and provides a strong rationale for blocking the IL-6 pathway in patients with CD37- B cell malignancies as a possible therapeutic intervention.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 2016

Volume

126

Issue

2

Start / End Page

653 / 666

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tetraspanins
  • Mice, Knockout
  • Mice, Inbred BALB C
  • Mice
  • Lymphoma, Large B-Cell, Diffuse
  • Interleukin-6
  • Immunology
  • Germinal Center
  • Cell Transformation, Neoplastic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
de Winde, C. M., Veenbergen, S., Young, K. H., Xu-Monette, Z. Y., Wang, X.-X., Xia, Y., … van Spriel, A. B. (2016). Tetraspanin CD37 protects against the development of B cell lymphoma. J Clin Invest, 126(2), 653–666. https://doi.org/10.1172/JCI81041
Winde, Charlotte M. de, Sharon Veenbergen, Ken H. Young, Zijun Y. Xu-Monette, Xiao-Xiao Wang, Yi Xia, Kausar J. Jabbar, et al. “Tetraspanin CD37 protects against the development of B cell lymphoma.J Clin Invest 126, no. 2 (February 2016): 653–66. https://doi.org/10.1172/JCI81041.
de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang X-X, Xia Y, et al. Tetraspanin CD37 protects against the development of B cell lymphoma. J Clin Invest. 2016 Feb;126(2):653–66.
de Winde, Charlotte M., et al. “Tetraspanin CD37 protects against the development of B cell lymphoma.J Clin Invest, vol. 126, no. 2, Feb. 2016, pp. 653–66. Pubmed, doi:10.1172/JCI81041.
de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang X-X, Xia Y, Jabbar KJ, van den Brand M, van der Schaaf A, Elfrink S, van Houdt IS, Gijbels MJ, van de Loo FAJ, Bennink MB, Hebeda KM, Groenen PJTA, van Krieken JH, Figdor CG, van Spriel AB. Tetraspanin CD37 protects against the development of B cell lymphoma. J Clin Invest. 2016 Feb;126(2):653–666.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 2016

Volume

126

Issue

2

Start / End Page

653 / 666

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tetraspanins
  • Mice, Knockout
  • Mice, Inbred BALB C
  • Mice
  • Lymphoma, Large B-Cell, Diffuse
  • Interleukin-6
  • Immunology
  • Germinal Center
  • Cell Transformation, Neoplastic