Tetraspanin CD37 protects against the development of B cell lymphoma

The Journal of Clinical Investigation
Charlotte M de WindeAnnemiek B van Spriel

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 ration...Continue Reading

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Citations

Dec 31, 2016·Blood·Francesco Bertoni, Anastasios Stathis
Apr 14, 2019·Blood Advances·Hakan KöksalSébastien Wälchli
Apr 21, 2017·Oncotarget·Aurelie Maisonial-BessetFrançoise Degoul
May 23, 2020·Medical Microbiology and Immunology·V E Dunlock
Aug 10, 2019·Frontiers in Immunology·Carlos CabañasAnnemiek B van Spriel
Aug 4, 2018·Frontiers in Immunology·Fagui ZouJianbo Sun
Jun 28, 2018·Frontiers in Immunology·Felipe Vences-Catalán, Shoshana Levy
Jun 14, 2018·Frontiers in Immunology·Fleur Schaper, Annemiek B van Spriel
Dec 19, 2020·International Journal of Molecular Sciences·Malgorzata BobrowiczMagdalena Winiarska
Sep 7, 2018·Journal of Cell Science·Charlotte M de WindeAnnemiek B van Spriel

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Methods Mentioned

BETA
chromosomal aberration
ubiquitination
flow cytometry
PCR
coimmunoprecipitation
confocal microscopy
biopsies
ELISA
FCS
transfection

Software Mentioned

CFX Manager
GraphPad Prism
Genemapper
GeneScan
JACoP
FlowJo
Odyssey
Fiji

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