TY - JOUR
T1 - High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites
AU - Elfrink, Suraya
AU - de Winde, Charlotte M.
AU - van den Brand, Michiel
AU - Berendsen, Madeleine
AU - Roemer, Margaretha G. M.
AU - Arnold, Frank
AU - Janssen, Luuk
AU - van der Schaaf, Alie
AU - Jansen, Erik
AU - Groenen, Patricia J. T. A.
AU - Eijkelenboom, Astrid
AU - Stevens, Wendy
AU - Hess, Corine J.
AU - van Krieken, J. Han
AU - Vermaat, Joost S. P.
AU - Cleven, Arjen H. G.
AU - de Groen, Ruben A. L.
AU - Neviani, Viviana
AU - de Jong, Daphne
AU - van Deventer, Sjoerd
AU - Scheijen, Blanca
AU - van Spriel, Annemiek B.
PY - 2019/9/19
Y1 - 2019/9/19
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072508540&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31366619
U2 - https://doi.org/10.1182/blood.2019001185
DO - https://doi.org/10.1182/blood.2019001185
M3 - Article
C2 - 31366619
SN - 0006-4971
VL - 134
SP - 946
EP - 950
JO - Blood
JF - Blood
IS - 12
ER -