Tetraspanin CD37 protects against the development of B cell lymphoma.
Journal Article (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
- PMC4731177
Electronic International Standard Serial Number (EISSN)
- 1558-8238
Digital Object Identifier (DOI)
- 10.1172/JCI81041
Language
- eng
Conference Location
- United States