Skip to main content

Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma.

Publication ,  Journal Article
Xu-Monette, ZY; Li, L; Byrd, JC; Jabbar, KJ; Manyam, GC; Maria de Winde, C; van den Brand, M; Tzankov, A; Visco, C; Wang, J; Dybkaer, K; Zu, Y ...
Published in: Blood
December 29, 2016

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 29, 2016

Volume

128

Issue

26

Start / End Page

3083 / 3100

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Tetraspanins
  • Survival Analysis
  • Risk Factors
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Protein Transport
  • Programmed Cell Death 1 Receptor
  • Prognosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu-Monette, Z. Y., Li, L., Byrd, J. C., Jabbar, K. J., Manyam, G. C., Maria de Winde, C., … Young, K. H. (2016). Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood, 128(26), 3083–3100. https://doi.org/10.1182/blood-2016-05-715094
Xu-Monette, Zijun Y., Ling Li, John C. Byrd, Kausar J. Jabbar, Ganiraju C. Manyam, Charlotte Maria de Winde, Michiel van den Brand, et al. “Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma.Blood 128, no. 26 (December 29, 2016): 3083–3100. https://doi.org/10.1182/blood-2016-05-715094.
Xu-Monette ZY, Li L, Byrd JC, Jabbar KJ, Manyam GC, Maria de Winde C, et al. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood. 2016 Dec 29;128(26):3083–100.
Xu-Monette, Zijun Y., et al. “Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma.Blood, vol. 128, no. 26, Dec. 2016, pp. 3083–100. Pubmed, doi:10.1182/blood-2016-05-715094.
Xu-Monette ZY, Li L, Byrd JC, Jabbar KJ, Manyam GC, Maria de Winde C, van den Brand M, Tzankov A, Visco C, Wang J, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WWL, Huh J, Ponzoni M, Ferreri AJM, Møller MB, Parsons BM, Winter JN, Wang M, Hagemeister FB, Piris MA, Han van Krieken J, Medeiros LJ, Li Y, van Spriel AB, Young KH. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood. 2016 Dec 29;128(26):3083–3100.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 29, 2016

Volume

128

Issue

26

Start / End Page

3083 / 3100

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Tetraspanins
  • Survival Analysis
  • Risk Factors
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Protein Transport
  • Programmed Cell Death 1 Receptor
  • Prognosis