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

Qing Ye; Zijun Y. Xu-Monette; Alexandar Tzankov; Lijuan Deng; Xiaoxiao Wang; Ganiraju C. Manyam; Carlo Visco; Santiago Montes-Moreno; Li Zhang; Karen Dybkær; April Chiu; Attilio Orazi; Youli Zu; Govind Bhagat; Kristy L. Richards; Eric D. Hsi; William W.L. Choi; J. Han van Krieken; Jooryung Huh; Maurilio Ponzoni; Andrés J.M. Ferreri; Ben M. Parsons; Michael B. Møller; Miguel A. Piris; Jane N. Winter; L. Jeffrey Medeiros; van den Shimin Hu; Ken H. Young

doi:10.18632/oncotarget.6262

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

Qing Ye, Zijun Y. Xu-Monette, Alexandar Tzankov, Lijuan Deng, Xiaoxiao Wang, Ganiraju C. Manyam, Carlo Visco, Santiago Montes-Moreno, Li Zhang, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han van Krieken, Jooryung Huh, Maurilio PonzoniAndrés J.M. Ferreri, Ben M. Parsons, Michael B. Møller, Miguel A. Piris, Jane N. Winter, L. Jeffrey Medeiros, van den Shimin Hu, Ken H. Young

Department of Pathology & Genomic Medicine

Research output: Contribution to journal › Article

50 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2401-2416
Number of pages	16
Journal	Oncotarget
Volume	7
Issue number	3
DOIs	https://doi.org/10.18632/oncotarget.6262
State	Published - 2016

Keywords

BCL2
BCL6
Diffuse large B-cell lymphoma
Double-hit
MYC

ASJC Scopus subject areas

Oncology

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Ye, Q., Xu-Monette, Z. Y., Tzankov, A., Deng, L., Wang, X., Manyam, G. C., Visco, C., Montes-Moreno, S., Zhang, L., Dybkær, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., van Krieken, J. H., Huh, J., ... Young, K. H. (2016). Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget, 7(3), 2401-2416. https://doi.org/10.18632/oncotarget.6262

Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. / Ye, Qing; Xu-Monette, Zijun Y.; Tzankov, Alexandar; Deng, Lijuan; Wang, Xiaoxiao; Manyam, Ganiraju C.; Visco, Carlo; Montes-Moreno, Santiago; Zhang, Li; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Parsons, Ben M.; Møller, Michael B.; Piris, Miguel A.; Winter, Jane N.; Medeiros, L. Jeffrey; Hu, van den Shimin; Young, Ken H.

In: Oncotarget, Vol. 7, No. 3, 2016, p. 2401-2416.

Research output: Contribution to journal › Article

Ye, Q, Xu-Monette, ZY, Tzankov, A, Deng, L, Wang, X, Manyam, GC, Visco, C, Montes-Moreno, S, Zhang, L, Dybkær, K, Chiu, A, Orazi, A, Zu, Y, Bhagat, G, Richards, KL, Hsi, ED, Choi, WWL, van Krieken, JH, Huh, J, Ponzoni, M, Ferreri, AJM, Parsons, BM, Møller, MB, Piris, MA, Winter, JN, Medeiros, LJ, Hu, VDS & Young, KH 2016, 'Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma', Oncotarget, vol. 7, no. 3, pp. 2401-2416. https://doi.org/10.18632/oncotarget.6262

Ye, Qing ; Xu-Monette, Zijun Y. ; Tzankov, Alexandar ; Deng, Lijuan ; Wang, Xiaoxiao ; Manyam, Ganiraju C. ; Visco, Carlo ; Montes-Moreno, Santiago ; Zhang, Li ; Dybkær, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Choi, William W.L. ; van Krieken, J. Han ; Huh, Jooryung ; Ponzoni, Maurilio ; Ferreri, Andrés J.M. ; Parsons, Ben M. ; Møller, Michael B. ; Piris, Miguel A. ; Winter, Jane N. ; Medeiros, L. Jeffrey ; Hu, van den Shimin ; Young, Ken H. / Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. In: Oncotarget. 2016 ; Vol. 7, No. 3. pp. 2401-2416.

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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.",

keywords = "BCL2, BCL6, Diffuse large B-cell lymphoma, Double-hit, MYC",

author = "Qing Ye and Xu-Monette, {Zijun Y.} and Alexandar Tzankov and Lijuan Deng and Xiaoxiao Wang and Manyam, {Ganiraju C.} and Carlo Visco and Santiago Montes-Moreno and Li Zhang and Karen Dybk{\ae}r and April Chiu and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L.} and Hsi, {Eric D.} and Choi, {William W.L.} and {van Krieken}, {J. Han} and Jooryung Huh and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J.M.} and Parsons, {Ben M.} and M{\o}ller, {Michael B.} and Piris, {Miguel A.} and Winter, {Jane N.} and Medeiros, {L. Jeffrey} and Hu, {van den Shimin} and Young, {Ken H.}",

year = "2016",

doi = "10.18632/oncotarget.6262",

language = "English (US)",

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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.

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