TY - JOUR
T1 - Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status
T2 - A report from an international DLBCL rituximab-CHOP consortium program study
AU - Visco, Carlo
AU - Tzankov, Alexander
AU - Xu-Monette, Zijun Y.
AU - Miranda, Roberto N.
AU - Tai, Yu Chuan
AU - Li, Yan
AU - Liu, Wei Min
AU - d'Amore, Emanuele S.G.
AU - Li, Yong
AU - Montes-Moreno, Santiago
AU - Dybkær, Karen
AU - Chiu, April
AU - Orazi, Attilio
AU - Zu, Youli
AU - Bhagat, Govind
AU - Wang, Huan You
AU - Dunphy, Cherie H.
AU - His, Eric D.
AU - Zhao, X. Frank
AU - Choi, William W.L.
AU - Zhao, Xiaoying
AU - Han van Krieken, J.
AU - Huang, Qin
AU - Ai, Weiyun
AU - O'Neill, Stacey
AU - Ponzoni, Maurilio
AU - Ferreri, Andres J.M.
AU - Kahl, Brad S.
AU - Winter, Jane N.
AU - Go, Ronald S.
AU - Dirnhofer, Stephan
AU - Piris, Miguel A.
AU - Møller, Michael B.
AU - Wu, Lin
AU - Medeiros, L. Jeffrey
AU - Young, Ken H.
PY - 2013/2/1
Y1 - 2013/2/1
N2 - Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated Bcell 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<0.0001). Bcl-2 protein overexpression was associated with inferior outcome in patients with germinal center subtype lymphoma, but multivariate analysis showed that this was dependent on BCL2 translocations. The gene expression profiling of patients with BCL2 rearrangements was unique, showing activation of pathways that were silent in the negative counterpart. BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions.
AB - Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated Bcell 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<0.0001). Bcl-2 protein overexpression was associated with inferior outcome in patients with germinal center subtype lymphoma, but multivariate analysis showed that this was dependent on BCL2 translocations. The gene expression profiling of patients with BCL2 rearrangements was unique, showing activation of pathways that were silent in the negative counterpart. BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions.
UR - http://www.scopus.com/inward/record.url?scp=84875314276&partnerID=8YFLogxK
U2 - 10.3324/haematol.2012.066209
DO - 10.3324/haematol.2012.066209
M3 - Article
C2 - 22929980
AN - SCOPUS:84875314276
SN - 0390-6078
VL - 98
SP - 255
EP - 263
JO - Haematologica
JF - Haematologica
IS - 2
ER -