Xu-Monette, ZY;
Li, L;
Byrd, JC;
Jabbar, KJ;
Manyam, GC;
de Winde, CM;
van den Brand, M;
... Young, KH; + view all
(2016)
Assessment of CD37 B-cell antigen and cell-of-origin significantly improves risk prediction in diffuse large B-cell lymphoma.
Blood
, 128
(26)
pp. 3083-3100.
10.1182/blood-2016-05-715094.
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Abstract
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37−) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell–like (GCB)/activated B-cell–like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37−, including TP53 mutation, NF-κBhigh, Mychigh, phosphorylated STAT3high, survivinhigh, p63−, and BCL6 translocation. CD37 positivity predicted superior survival, abolishing the prognostic impact of high IPI and above biomarkers in GCB-DLBCL but not in ABC-DLBCL. Combining risk scores for CD37− status and ABC cell of origin with the IPI, defined as molecularly adjusted IPI for R-CHOP (M-IPI-R), or IPI plus immunohistochemistry (IHC; IPI+IHC) for CD37, Myc, and Bcl-2, significantly improved risk prediction over IPI alone. Gene expression profiling suggested that decreased CD20 and increased PD-1 levels in CD37− DLBCL, ICOSLG upregulation in CD37+ GCB-DLBCL, and CD37 functions during R-CHOP treatment underlie the pivotal role of CD37 status in clinical outcomes. In conclusion, CD37 is a critical determinant of R-CHOP outcome in DLBCL especially in GCB-DLBCL, representing its importance for optimal rituximab action and sustained immune responses. The combined molecular and clinical prognostic indices, M-IPI-R and IPI+IHC, have remarkable predictive values in R-CHOP–treated DLBCL.
| Type: | Article |
|---|---|
| Title: | Assessment of CD37 B-cell antigen and cell-of-origin significantly improves risk prediction in diffuse large B-cell lymphoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1182/blood-2016-05-715094 |
| Publisher version: | http://doi.org/10.1182/blood-2016-05-715094 |
| Language: | English |
| Additional information: | © 2016 by The American Society of Hematology. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CD37, DLBCL, M-IPI-R, PD-1, ICOSLG, COO, IPI, R-CHOP, rituximab, CD20, CTLA-4, GCB, ABC |
| 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-pp.ucl.ac.uk/id/eprint/1556643 |
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