Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: A report from an international DLBCL rituximab-CHOP consortium program study Journal Article

   

Authors:	Visco, C.; Tzankov, A.; Xu-Monette, Z. Y.; Miranda, R. N.; Tai, Y. C.; Li, Y.; Liu, W. M.; d'Amore, E. S. G.; Montes-Moreno, S.; Dybkær, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Wang, H. Y.; Dunphy, C. H.; His, E. D.; Zhao, X. F.; Choi, W. W. L.; Zhao, X.; Han van Krieken, J.; Huang, Q.; Ai, W.; O'Neill, S.; Ponzoni, M.; Ferreri, A. J. M.; Kahl, B. S.; Winter, J. N.; Go, R. S.; Dirnhofer, S.; Piris, M. A.; Møller, M. B.; Wu, L.; Medeiros, L. J.; Young, K. H.
Article Title:	Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: A report from an international DLBCL rituximab-CHOP consortium program study
Abstract:	Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated Bcell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has been questioned in the new therapeutic era. We analyzed Bcl-2 protein expression, and BCL2 and MYC gene abnormalities by interphase fluorescence in situ hybridization in 327 patients with de novo disease treated with rituximab-CHOP. Isolated BCL2 and MYC rearrangements were not predictive of outcome in our patients as a whole, but only in those with the germinal center subtype of lymphoma. The prognostic relevance of isolated MYC rearrangements was weaker than that of BCL2 isolated translocations, but was probably limited by the rarity of the rearrangements. Seven of eight patients with double hit lymphoma had the germinal center subtype with poor outcome. The germinal center subtype patients with isolated BCL2 translocations had significantly worse outcome than the patients without BCL2 rearrangements (P=0.0002), and their outcome was similar to that of patients with the activated B-cell subtype (P=0.30), but not as bad as the outcome of patients with double hit lymphoma (P<0.0001). Bcl-2 protein overexpression was associated with inferior outcome in patients with germinal center subtype lymphoma, but multivariate analysis showed that this was dependent on BCL2 translocations. The gene expression profiling of patients with BCL2 rearrangements was unique, showing activation of pathways that were silent in the negative counterpart. BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions. ©2013 Ferrata Storti Foundation.
Keywords:	immunohistochemistry; adult; human tissue; protein expression; aged; major clinical study; overall survival; prednisone; doxorubicin; validation process; cancer radiotherapy; rituximab; outcome assessment; progression free survival; multiple cycle treatment; gene expression profiling; cyclophosphamide; vincristine; fluorescence in situ hybridization; bcl2 related protein a1; myc protein; chromosome rearrangement; large cell lymphoma; oncogene myc; cancer prognosis
Journal Title:	Haematologica
Volume:	98
Issue:	2
ISSN:	0390-6078
Publisher:	Ferrata Storti Foundation
Date Published:	2013-02-01
Start Page:	255
End Page:	263
Language:	English
PROVIDER:	scopus
PMCID:	PMC3561433
PUBMED:	22929980
DOI:	10.3324/haematol.2012.066209
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84875314276&partnerID=40&md5=b3383498d313b84245ebe4233fcec6a9
Notes:	--- - "Export Date: 1 May 2013" - "CODEN: HAEMA" - ":doi 10.3324/haematol.2012.066209" - ": Chemicals/CAScyclophosphamide, 50-18-0; doxorubicin, 23214-92-8, 25316-40-9; prednisone, 53-03-2; rituximab, 174722-31-7; vincristine, 57-22-7" - "Source: Scopus"

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