Tetraspanin CD37 protects against the development of B cell lymphoma.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 2016

Published In

Volume / Issue

  • 126 / 2

Start / End Page

  • 653 - 666

PubMed ID

  • 26784544

Pubmed Central ID

  • 26784544

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI81041

Language

  • eng