TY - JOUR
T1 - Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma
AU - Ye, Qing
AU - Xu-Monette, Zijun Y.
AU - Tzankov, Alexandar
AU - Deng, Lijuan
AU - Wang, Xiaoxiao
AU - Manyam, Ganiraju C.
AU - Visco, Carlo
AU - Montes-Moreno, Santiago
AU - Zhang, Li
AU - Dybkær, Karen
AU - Chiu, April
AU - Orazi, Attilio
AU - Zu, Youli
AU - Bhagat, Govind
AU - Richards, Kristy L.
AU - Hsi, Eric D.
AU - Choi, William W.L.
AU - van Krieken, J. Han
AU - Huh, Jooryung
AU - Ponzoni, Maurilio
AU - Ferreri, Andrés J.M.
AU - Parsons, Ben M.
AU - Møller, Michael B.
AU - Piris, Miguel A.
AU - Winter, Jane N.
AU - Medeiros, L. Jeffrey
AU - Hu, van den Shimin
AU - Young, Ken H.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - BCL2
KW - BCL6
KW - Diffuse large B-cell lymphoma
KW - Double-hit
KW - MYC
UR - http://www.scopus.com/inward/record.url?scp=84962327229&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962327229&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6262
DO - 10.18632/oncotarget.6262
M3 - Article
C2 - 26573234
AN - SCOPUS:84962327229
VL - 7
SP - 2401
EP - 2416
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 3
ER -