Elfrink, S;
De Winde, CM;
van den Brand, M;
Berendsen, M;
Roemer, MGM;
Arnold, F;
Janssen, L;
... van Spriel, AB; + view all
(2019)
High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites.
Blood
, 134
(12)
pp. 946-950.
10.1182/blood.2019001185.
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Text (Article)
Accepted manuscript incl figures CD37 mutations in IP-DLBCL_BLD-2019-001185.pdf - Accepted Version Download (2MB) | Preview |
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Text (Supplementary Information)
Supplementary information CD37 mutations in IP-DLBCL_BLD-2019-001185.pdf - Accepted Version Download (10MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1182/blood.2019001185 |
| Publisher version: | https://doi.org/10.1182/blood.2019001185 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | diffuse large b-cell lymphoma, lymphoma, mutation, pan-hematopoietic expression protein, mutation analysis, b-lymphocytes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10078632 |
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