Haematologica (Feb 2013)
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
- Carlo Visco,
- Alexander Tzankov,
- Zijun Y. Xu-Monette,
- Roberto N. Miranda,
- Yu Chuan Tai,
- Yan Li,
- Wei-min Liu,
- Emanuele S. G. d'Amore,
- Yong Li,
- Santiago Montes-Moreno,
- Karen Dybkær,
- April Chiu,
- Attilio Orazi,
- Youli Zu,
- Govind Bhagat,
- Huan-You Wang,
- Cherie H. Dunphy,
- Eric D. His,
- X. Frank Zhao,
- William WL. Choi,
- Xiaoying Zhao,
- J. Han van Krieken,
- Qin Huang,
- Weiyun Ai,
- Stacey O'Neill,
- Maurilio Ponzoni,
- Andres JM. Ferreri,
- Brad S. Kahl,
- Jane N. Winter,
- Ronald S. Go,
- Stephan Dirnhofer,
- Miguel A. Piris,
- Michael B. Møller,
- Lin Wu,
- L. Jeffrey Medeiros,
- Ken H. Young
Affiliations
- Carlo Visco
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;San Bortolo Hospital, Vicenza, Italy
- Alexander Tzankov
- University Hospital, Basel, Switzerland
- Zijun Y. Xu-Monette
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Roberto N. Miranda
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Yu Chuan Tai
- Roche Molecular Systems, Inc., Pleasanton, CA, USA
- Yan Li
- Roche Molecular Systems, Inc., Pleasanton, CA, USA
- Wei-min Liu
- Roche Molecular Systems, Inc., Pleasanton, CA, USA
- Emanuele S. G. d'Amore
- San Bortolo Hospital, Vicenza, Italy
- Yong Li
- University of Louisville School of Medicine, Louisville, KY, USA
- Santiago Montes-Moreno
- Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain
- Karen Dybkær
- Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
- April Chiu
- Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- Attilio Orazi
- Weill Medical College of Cornell University, New York, NY, USA
- Youli Zu
- The Methodist Hospital, Houston, TX, USA
- Govind Bhagat
- Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA
- Huan-You Wang
- University of California San Diego School of Medicine, San Diego, CA, USA
- Cherie H. Dunphy
- University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Eric D. His
- Cleveland Clinic, Cleveland, OH, USA
- X. Frank Zhao
- University of Maryland School of Medicine, Baltimore, MD, USA
- William WL. Choi
- University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China
- Xiaoying Zhao
- Zhejiang University School of Medicine, Second University Hospital, Hangzhou, China
- J. Han van Krieken
- Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
- Qin Huang
- City of Hope National Medical Center, Los Angeles, CA, USA
- Weiyun Ai
- University of California San Francisco School of Medicine, San Francisco, CA, USA
- Stacey O'Neill
- University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Maurilio Ponzoni
- San Raffaele H. Scientific Institute, Milan, Italy
- Andres JM. Ferreri
- San Raffaele H. Scientific Institute, Milan, Italy
- Brad S. Kahl
- University of Wisconsin Hospital and Clinic, Madison, WI, USA
- Jane N. Winter
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Ronald S. Go
- Gundersen Lutheran Health System, La Crosse, WI, USA
- Stephan Dirnhofer
- University Hospital, Basel, Switzerland
- Miguel A. Piris
- Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain
- Michael B. Møller
- Odense University Hospital, Odense, Denmark
- Lin Wu
- Roche Molecular Systems, Inc., Pleasanton, CA, USA
- L. Jeffrey Medeiros
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Ken H. Young
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- DOI
- https://doi.org/10.3324/haematol.2012.066209
- Journal volume & issue
-
Vol. 98,
no. 2
Abstract
Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell 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
