Prognostic impact of concurrent <i>MYC</i> and <i>BCL6</i> rearrangements and expression in <i>de novo</i> diffuse large B-cell lymphoma

Abstract

// Qing Ye 1,* , Zijun Y. Xu-Monette 1,* , Alexandar Tzankov 2,* , Lijuan Deng 1 , Xiaoxiao Wang 1 , Ganiraju C. Manyam 3 , Carlo Visco 4 , Santiago Montes-Moreno 5 , Li Zhang 3 , Karen Dybk&aelig;r 6 , April Chiu 7 , Attilio Orazi 8 , Youli Zu 9 , Govind Bhagat 10 , Kristy L. Richards 11 , Eric D. Hsi 12 , William W.L. Choi 13 , J. Han van Krieken 14 , Jooryung Huh 15 , Maurilio Ponzoni 16 , Andr&eacute;s J.M. Ferreri 16 , Ben M. Parsons 17 , Michael B. M&oslash;ller 18 , Miguel A. Piris 5 , Jane N. Winter 19 , L. Jeffrey Medeiros 1 Shimin Hu 1 and Ken H. Young 1,20 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 University Hospital, Basel, Switzerland 3 Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 San Bortolo Hospital, Vicenza, Italy 5 Hospital Universitario Marques de Valdecilla, Santander, Spain 6 Aalborg University Hospital, Aalborg, Denmark 7 Memorial Sloan-Kettering Cancer Center, New York, New York, USA 8 Weill Medical College of Cornell University, New York, New York, USA 9 Houston Methodist Hospital, Houston, Texas, USA 10 Columbia University Medical Center and New York Presbyterian Hospital, New York, New York, USA 11 University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA 12 Cleveland Clinic, Cleveland, Ohio, USA 13 University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China 14 Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 15 Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea 16 San Raffaele H. Scientific Institute, Milan, Italy 17 Gundersen Lutheran Health System, La Crosse, Wisconsin, USA 18 Odense University Hospital, Odense, Denmark 19 Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA 20 The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, Texas, USA * These authors have contributed equally to this work Correspondence to: Ken H. Young, email: // Keywords : diffuse large B-cell lymphoma, double-hit, MYC, BCL6, BCL2 Received : August 28, 2015 Accepted : September 09, 2015 Published : November 12, 2015 Abstract Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2 , BCL6 , or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC , BCL2 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination with MYC translocation (observed in 2.0% of diffuse large B-cell lymphoma) predicted poorer survival in diffuse large B-cell lymphoma patients. Diffuse large B-cell lymphoma patients with MYC/BCL6 co-expression did have significantly poorer survival, however, MYC/BCL6 co-expression had no effect on prognosis in the absence of MYC/BCL2 co-expression, and had no additive impact in MYC + /BCL2 + cases. The isolated MYC + /BCL6 + /BCL2 &minus; subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC + /BCL2 + /BCL6 &minus; subset (more frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma needs to be refined based on the specific genetic abnormalities present in these tumors.