title: Tetraspanin CD37 protects against the development of B cell lymphoma.
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.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: de Winde
authors.forename: Sharon
authors.initials: S
authors.lastname: Veenbergen
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Kausar J
authors.initials: KJ
authors.lastname: Jabbar
authors.forename: Michiel
authors.initials: M
authors.lastname: van den Brand
authors.forename: Alie
authors.initials: A
authors.lastname: van der Schaaf
authors.forename: Suraya
authors.initials: S
authors.lastname: Elfrink
authors.forename: Inge S
authors.initials: IS
authors.lastname: van Houdt
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Fons A J
authors.initials: FA
authors.lastname: van de Loo
authors.forename: Miranda B
authors.initials: MB
authors.lastname: Bennink
authors.forename: Konnie M
authors.initials: KM
authors.lastname: Hebeda
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504565:Cd37 protein, mouse; D015850:Interleukin-6; D059470:Tetraspanins; D025521:Tumor Suppressor Proteins