Year: 2016
Type: article
Abstract: 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.
DOI: 10.1172/jci81041
Authors: Charlotte M. de Winde, Sharon Veenbergen, Ken H. Young, Zijun Y. Xu-Monette, Xiao-xiao Wang, Yi Xia, Kausar J. Jabbar, Michiel van den Brand, Alie van der Schaaf, Suraya Elfrink, Inge S. van Houdt, Marion J. Gijbels, Fons A.J. van de Loo, Miranda B. Bennink, Konnie M. Hebeda, Patricia J.T.A. Groenen, J. Han van Krieken, Carl G. Figdor, Annemiek B. van Spriel
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Monash University, Radboud Universiteit, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, KWF Kankerbestrijding, Radboud Universitair Medisch Centrum, National Institutes of Health, University of Texas MD Anderson Cancer Center, Erasmus Universitair Medisch Centrum Rotterdam, National Cancer Institute, FP7 Ideas: European Research Council
Awards: G1065855647, G2751214453, G2786947382, MYC as a Biomarker in Aggressive Non-Hodgkin Lymphoma, G3309929535, G4536930479, M. D. Anderson Cancer Center SPORE in Multiple Myeloma, Convergence of MicroRNAs and p53 Signaling in Multiple Myeloma: Environmental Co, UT M.D. Anderson Cancer Center Lymphoma SPORE, Mimicking pathogens; an integrated nano-medicine approach to developing intelligent cancer vaccines.
OpenAlex ID: W2243979166