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 Deventer & 2 others Blanca 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
Elfrink, Suraya ; de Winde, Charlotte M. ; van den Brand, Michiel ; Berendsen, Madeleine ; Roemer, Margaretha G. M. ; Arnold, Frank ; Janssen, Luuk ; van der Schaaf, Alie ; Jansen, Erik ; Groenen, Patricia J. T. A. ; Eijkelenboom, Astrid ; Stevens, Wendy ; Hess, Corine J. ; van Krieken, J. Han ; Vermaat, Joost S. P. ; Cleven, Arjen H. G. ; de Groen, Ruben A. L. ; Neviani, Viviana ; de Jong, Daphne ; van Deventer, Sjoerd ; Scheijen, Blanca ; van Spriel, Annemiek B. / High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites. In: Blood. 2019 ; Vol. 134, No. 12. pp. 946-950.
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title = "High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites",
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.",
author = "Suraya Elfrink and {de Winde}, {Charlotte M.} and {van den Brand}, Michiel and Madeleine Berendsen and Roemer, {Margaretha G. M.} and Frank Arnold and Luuk Janssen and {van der Schaaf}, Alie and Erik Jansen and Groenen, {Patricia J. T. A.} and Astrid Eijkelenboom and Wendy Stevens and Hess, {Corine J.} and {van Krieken}, {J. Han} and Vermaat, {Joost S. P.} and Cleven, {Arjen H. G.} and {de Groen}, {Ruben A. L.} and Viviana Neviani and {de Jong}, Daphne and {van Deventer}, Sjoerd and Blanca Scheijen and {van Spriel}, {Annemiek B.}",
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Elfrink, S, de Winde, CM, van den Brand, M, Berendsen, M, Roemer, MGM, Arnold, F, Janssen, L, van der Schaaf, A, Jansen, E, Groenen, PJTA, Eijkelenboom, A, Stevens, W, Hess, CJ, van Krieken, JH, Vermaat, JSP, Cleven, AHG, de Groen, RAL, Neviani, V, de Jong, D, van Deventer, S, Scheijen, B & van Spriel, AB 2019, 'High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites' Blood, vol. 134, no. 12, pp. 946-950. https://doi.org/10.1182/blood.2019001185

High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites. / Elfrink, Suraya; de Winde, Charlotte M.; van den Brand, Michiel; Berendsen, Madeleine; Roemer, Margaretha G. M.; Arnold, Frank; Janssen, Luuk; van der Schaaf, Alie; Jansen, Erik; Groenen, Patricia J. T. A.; Eijkelenboom, Astrid; Stevens, Wendy; Hess, Corine J.; van Krieken, J. Han; Vermaat, Joost S. P.; Cleven, Arjen H. G.; de Groen, Ruben A. L.; Neviani, Viviana; de Jong, Daphne; van Deventer, Sjoerd; Scheijen, Blanca; van Spriel, Annemiek B.

In: Blood, Vol. 134, No. 12, 19.09.2019, p. 946-950.

Research output: Contribution to journalArticleAcademicpeer-review

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31366619

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DO - 10.1182/blood.2019001185

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JF - Blood

SN - 0006-4971

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