Journal
BLOOD
Volume 132, Issue 12, Pages 946-950Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019001185
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Funding
- Radboudumc grant
- Netherlands Organization for Scientific Research [019.162LW.004, ICI024.002.009]
- Stichting Fonds Oncologie Holland
- Netherlands Organization for Scientific Research grant (NWO-ALW VIDI grant) [864.11.006]
- Dutch Cancer Society [KUN2014-6845]
- European Research Council [724281]
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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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