title: BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma.
abstract: 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.
authors.affiliation: Leukemia/Lymphoma Molecular Profiling Project, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Vishala T
authors.initials: VT
authors.lastname: Neppalli
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Bhavana J
authors.initials: BJ
authors.lastname: Dave
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: James
authors.initials: J
authors.lastname: Lynch
authors.forename: Christine P
authors.initials: CP
authors.lastname: Hans
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm