BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma.
BACKGROUND
The role of BCL2 as a predictor of survival in diffuse large B-cell lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL, as well as primary mediastinal DLBCL.


METHODS
In this study, we investigated the correlation of BCL2 expression with survival in the two major subgroups of DLBCL, as well as the mechanisms of BCL2 expression.


RESULTS
There was no significant correlation between BCL2 protein expression and overall survival within the GCB subgroup, but BCL2 expression had a significant adverse effect on overall survival within the ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P < .04). The difference remained significant when the analyses were performed at different cutoff values. The t(14;18) was frequently observed in the GCB subgroup and was highly associated with BCL2 expression. Patients with ABC DLBCL did not exhibit t(14;18) but had a markedly higher frequency of chromosome 18q21 amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21 amplification or activation of the nuclear factor-kappa B pathway, as reported previously, seem to be mainly responsible for the upregulation of BCL2 expression in the ABC subgroup.


CONCLUSIONS
Treating all DLBCL as a single entity ignores the mechanistic differences in BCL2 upregulation and obscures the prognostic significance of BCL2 expression. Hence, the significance of BCL2 and other biomarkers should be assessed in the context of DLBCL subgroups in future studies.
Iqbal
Javeed
J
Leukemia/Lymphoma Molecular Profiling Project, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Neppalli
Vishala T
VT
Wright
George
G
Dave
Bhavana J
BJ
Horsman
Douglas E
DE
Rosenwald
Andreas
A
Lynch
James
J
Hans
Christine P
CP
Weisenburger
Dennis D
DD
Greiner
Timothy C
TC
Gascoyne
Randy D
RD
Campo
Elias
E
Ott
German
G
Müller-Hermelink
H Konrad
HK
Delabie
Jan
J
Jaffe
Elaine S
ES
Grogan
Thomas M
TM
Connors
Joseph M
JM
Vose
Julie M
JM
Armitage
James O
JO
Staudt
Louis M
LM
Chan
Wing C
WC
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002887:Chromosomes, Human, Pair 18; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016019:Survival Analysis; D014178:Translocation, Genetic; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm