title: Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma.
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- 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- 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.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: University Hospital, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ganiraju C
authors.initials: GC
authors.lastname: Manyam
authors.affiliation: San Bortolo Hospital, Vicenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.affiliation: Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.affiliation: Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkær
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.affiliation: Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Columbia University Medical Center and New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.affiliation: Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.affiliation: University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China.
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.affiliation: Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea.
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.affiliation: San Raffaele H. Scientific Institute, Milan, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: San Raffaele H. Scientific Institute, Milan, Italy.
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.affiliation: Gundersen Lutheran Health System, La Crosse, Wisconsin, USA.
authors.forename: Ben M
authors.initials: BM
authors.lastname: Parsons
authors.affiliation: Odense University Hospital, Odense, Denmark.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
authors.affiliation: Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, Texas, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000069283:Rituximab; D014178:Translocation, Genetic; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C084103:BCL6 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: BCL2; BCL6; MYC; diffuse large B-cell lymphoma; double-hit