Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma

Kenneth Offit, Francesco Lo Coco, Diane C. Louie, Nasser Z. Parsa, Denis Leung, Carol Portlock, B. Hilda Ye, Florigio Lista, Daniel A. Filippa, Ayala Rosenbaum, Marc Ladanyi, Suresh Jhanwar, Riccardo Dalla-Favera, R. S K Chaganti

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

Background. About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC. Methods. We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome. Results. Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the pro-portion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs. Conclusions. Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalNew England Journal of Medicine
Volume331
Issue number2
StatePublished - Jul 14 1994
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Genes
Lymphoma
Confidence Intervals
Non-Hodgkin's Lymphoma
Disease Progression
bcl-2 Genes
Proto-Oncogenes
Gene Rearrangement
Cellular Structures
Southern Blotting
Treatment Failure
L-Lactate Dehydrogenase
Germ Cells
Cytogenetics
B-Lymphocytes
Biomarkers
Bone Marrow
Survival
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Offit, K., Lo Coco, F., Louie, D. C., Parsa, N. Z., Leung, D., Portlock, C., ... Chaganti, R. S. K. (1994). Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. New England Journal of Medicine, 331(2), 74-80.

Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. / Offit, Kenneth; Lo Coco, Francesco; Louie, Diane C.; Parsa, Nasser Z.; Leung, Denis; Portlock, Carol; Ye, B. Hilda; Lista, Florigio; Filippa, Daniel A.; Rosenbaum, Ayala; Ladanyi, Marc; Jhanwar, Suresh; Dalla-Favera, Riccardo; Chaganti, R. S K.

In: New England Journal of Medicine, Vol. 331, No. 2, 14.07.1994, p. 74-80.

Research output: Contribution to journalArticle

Offit, K, Lo Coco, F, Louie, DC, Parsa, NZ, Leung, D, Portlock, C, Ye, BH, Lista, F, Filippa, DA, Rosenbaum, A, Ladanyi, M, Jhanwar, S, Dalla-Favera, R & Chaganti, RSK 1994, 'Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma', New England Journal of Medicine, vol. 331, no. 2, pp. 74-80.
Offit K, Lo Coco F, Louie DC, Parsa NZ, Leung D, Portlock C et al. Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. New England Journal of Medicine. 1994 Jul 14;331(2):74-80.
Offit, Kenneth ; Lo Coco, Francesco ; Louie, Diane C. ; Parsa, Nasser Z. ; Leung, Denis ; Portlock, Carol ; Ye, B. Hilda ; Lista, Florigio ; Filippa, Daniel A. ; Rosenbaum, Ayala ; Ladanyi, Marc ; Jhanwar, Suresh ; Dalla-Favera, Riccardo ; Chaganti, R. S K. / Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. In: New England Journal of Medicine. 1994 ; Vol. 331, No. 2. pp. 74-80.
@article{b2ccddd212324e42841eb08bb4f88b1e,
title = "Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma",
abstract = "Background. About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC. Methods. We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome. Results. Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the pro-portion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs. Conclusions. Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma.",
author = "Kenneth Offit and {Lo Coco}, Francesco and Louie, {Diane C.} and Parsa, {Nasser Z.} and Denis Leung and Carol Portlock and Ye, {B. Hilda} and Florigio Lista and Filippa, {Daniel A.} and Ayala Rosenbaum and Marc Ladanyi and Suresh Jhanwar and Riccardo Dalla-Favera and Chaganti, {R. S K}",
year = "1994",
month = "7",
day = "14",
language = "English (US)",
volume = "331",
pages = "74--80",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "2",

}

TY - JOUR

T1 - Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma

AU - Offit, Kenneth

AU - Lo Coco, Francesco

AU - Louie, Diane C.

AU - Parsa, Nasser Z.

AU - Leung, Denis

AU - Portlock, Carol

AU - Ye, B. Hilda

AU - Lista, Florigio

AU - Filippa, Daniel A.

AU - Rosenbaum, Ayala

AU - Ladanyi, Marc

AU - Jhanwar, Suresh

AU - Dalla-Favera, Riccardo

AU - Chaganti, R. S K

PY - 1994/7/14

Y1 - 1994/7/14

N2 - Background. About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC. Methods. We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome. Results. Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the pro-portion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs. Conclusions. Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma.

AB - Background. About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC. Methods. We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome. Results. Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the pro-portion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs. Conclusions. Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma.

UR - http://www.scopus.com/inward/record.url?scp=0028227464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028227464&partnerID=8YFLogxK

M3 - Article

C2 - 8208268

AN - SCOPUS:0028227464

VL - 331

SP - 74

EP - 80

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 2

ER -