BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma

Javeed Iqbal, Vishala T. Neppalli, George Wright, Bhavana J. Dave, Douglas E. Horsman, Andreas Rosenwald, James Lynch, Christine P. Hans, Dennis D. Weisenburger, Timothy C. Greiner, Randy D. Gascoyne, Elias Campo, German Ott, H. Konrad Müller-Hermelink, Jan Delabie, Elaine S. Jaffe, Thomas M. Grogan, Joseph M. Connors, Julie M. Vose, James O. ArmitageLouis M. Staudt, Wing C. Chan

Research output: Contribution to journalArticle

221 Citations (Scopus)

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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)961-968
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number6
DOIs
StatePublished - Feb 20 2006

Fingerprint

Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Germinal Center
Survival
Proto-Oncogene Proteins c-bcl-2
Up-Regulation
NF-kappa B
Chromosomes
Biomarkers
Messenger RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. / Iqbal, Javeed; Neppalli, Vishala T.; Wright, George; Dave, Bhavana J.; Horsman, Douglas E.; Rosenwald, Andreas; Lynch, James; Hans, Christine P.; Weisenburger, Dennis D.; Greiner, Timothy C.; Gascoyne, Randy D.; Campo, Elias; Ott, German; Müller-Hermelink, H. Konrad; Delabie, Jan; Jaffe, Elaine S.; Grogan, Thomas M.; Connors, Joseph M.; Vose, Julie M.; Armitage, James O.; Staudt, Louis M.; Chan, Wing C.

In: Journal of Clinical Oncology, Vol. 24, No. 6, 20.02.2006, p. 961-968.

Research output: Contribution to journalArticle

Iqbal, J, Neppalli, VT, Wright, G, Dave, BJ, Horsman, DE, Rosenwald, A, Lynch, J, Hans, CP, Weisenburger, DD, Greiner, TC, Gascoyne, RD, Campo, E, Ott, G, Müller-Hermelink, HK, Delabie, J, Jaffe, ES, Grogan, TM, Connors, JM, Vose, JM, Armitage, JO, Staudt, LM & Chan, WC 2006, 'BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma', Journal of Clinical Oncology, vol. 24, no. 6, pp. 961-968. https://doi.org/10.1200/JCO.2005.03.4264
Iqbal, Javeed ; Neppalli, Vishala T. ; Wright, George ; Dave, Bhavana J. ; Horsman, Douglas E. ; Rosenwald, Andreas ; Lynch, James ; Hans, Christine P. ; Weisenburger, Dennis D. ; Greiner, Timothy C. ; Gascoyne, Randy D. ; Campo, Elias ; Ott, German ; Müller-Hermelink, H. Konrad ; Delabie, Jan ; Jaffe, Elaine S. ; Grogan, Thomas M. ; Connors, Joseph M. ; Vose, Julie M. ; Armitage, James O. ; Staudt, Louis M. ; Chan, Wing C. / BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 6. pp. 961-968.
@article{94c02d22a60e4d7889feadb9ebcd4502,
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. Patients and 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. Conclusion: 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.",
author = "Javeed Iqbal and Neppalli, {Vishala T.} and George Wright and Dave, {Bhavana J.} and Horsman, {Douglas E.} and Andreas Rosenwald and James Lynch and Hans, {Christine P.} and Weisenburger, {Dennis D.} and Greiner, {Timothy C.} and Gascoyne, {Randy D.} and Elias Campo and German Ott and M{\"u}ller-Hermelink, {H. Konrad} and Jan Delabie and Jaffe, {Elaine S.} and Grogan, {Thomas M.} and Connors, {Joseph M.} and Vose, {Julie M.} and Armitage, {James O.} and Staudt, {Louis M.} and Chan, {Wing C.}",
year = "2006",
month = "2",
day = "20",
doi = "10.1200/JCO.2005.03.4264",
language = "English (US)",
volume = "24",
pages = "961--968",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma

AU - Iqbal, Javeed

AU - Neppalli, Vishala T.

AU - Wright, George

AU - Dave, Bhavana J.

AU - Horsman, Douglas E.

AU - Rosenwald, Andreas

AU - Lynch, James

AU - Hans, Christine P.

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy C.

AU - Gascoyne, Randy D.

AU - Campo, Elias

AU - Ott, German

AU - Müller-Hermelink, H. Konrad

AU - Delabie, Jan

AU - Jaffe, Elaine S.

AU - Grogan, Thomas M.

AU - Connors, Joseph M.

AU - Vose, Julie M.

AU - Armitage, James O.

AU - Staudt, Louis M.

AU - Chan, Wing C.

PY - 2006/2/20

Y1 - 2006/2/20

N2 - 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. Patients and 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. Conclusion: 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.

AB - 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. Patients and 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. Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=33644896809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644896809&partnerID=8YFLogxK

U2 - 10.1200/JCO.2005.03.4264

DO - 10.1200/JCO.2005.03.4264

M3 - Article

C2 - 16418494

AN - SCOPUS:33644896809

VL - 24

SP - 961

EP - 968

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -