High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

Suraya Elfrink, Charlotte M. de Winde, Michiel van den Brand, Madeleine Berendsen, Margaretha G. M. Roemer, Frank Arnold, Luuk Janssen, Alie van der Schaaf, Erik Jansen, Patricia J. T. A. Groenen, Astrid Eijkelenboom, Wendy Stevens, Corine J. Hess, J. Han van Krieken, Joost S. P. Vermaat, Arjen H. G. Cleven, Ruben A. L. de Groen, Viviana Neviani, Daphne de Jong, Sjoerd van DeventerBlanca Scheijen, Annemiek B. van Spriel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Tetraspanin CD37 is predominantly expressed on the cell surface of mature B lymphocytes and is currently being studied as novel therapeutic target for B-cell lymphoma. Recently, we demonstrated that loss of CD37 induces spontaneous B-cell lymphoma in Cd37-knockout mice and correlates with inferior survival in patients with diffuse large B-cell lymphoma (DLBCL). Here, CD37 mutation analysis was performed in a cohort of 137 primary DLBCL samples, including 44 primary immune-privileged site-associated DLBCL (IP-DLBCL) samples originating in the testis or central nervous system. CD37 mutations were exclusively identified in IP-DLBCL cases (10/44, 23%) but absent in non-IP-DLBCL cases. The aberrations included 10 missense mutations, 1 deletion, and 3 splice-site CD37 mutations. Modeling and functional analysis of CD37 missense mutations revealed loss of function by impaired CD37 protein expression at the plasma membrane of human lymphoma B cells. This study provides novel insight into the molecular pathogenesis of IP-DLBCL and indicates that anti-CD37 therapies will be more beneficial for DLBCL patients without CD37 mutations.
Original languageEnglish
Pages (from-to)946-950
Number of pages5
JournalBlood
Volume134
Issue number12
DOIs
Publication statusPublished - 19 Sep 2019

Cite this

Elfrink, S., de Winde, C. M., van den Brand, M., Berendsen, M., Roemer, M. G. M., Arnold, F., ... van Spriel, A. B. (2019). High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites. Blood, 134(12), 946-950. https://doi.org/10.1182/blood.2019001185