The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma

Kerry J. Savage, Stefano Monti, Jeffery L. Kutok, Giorgio Cattoretti, Donna Neuberg, Laurence De Leval, Paul Kurtin, Paola Dal Cin, Christine Ladd, Friedrich Feuerhake, Ricardo C T Aguiar, Sigui Li, Gilles Salles, Francoise Berger, Wen Jing, Geraldine S. Pinkus, Thomas Matthew Habermann, Riccardo Dalla-Favera, Nancy Lee Harris, Jon C. Aster & 2 others Todd R. Golub, Margaret A. Shipp

Research output: Contribution to journalArticle

631 Citations (Scopus)

Abstract

Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in ML-BCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-κB (NF-κB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-κB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.

Original languageEnglish (US)
Pages (from-to)3871-3879
Number of pages9
JournalBlood
Volume102
Issue number12
DOIs
StatePublished - Dec 1 2003

Fingerprint

Lymphoma, Large B-Cell, Diffuse
TNF Receptor-Associated Factor 1
B-Cell Lymphoma
Hodgkin Disease
STAT1 Transcription Factor
Cells
Interleukin-13 Receptors
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Janus Kinase 2
Interleukin-13
Gene expression
Tumors
Classifiers
Tumor Necrosis Factor-alpha
Chemical activation
Reed-Sternberg Cells
Sclerosis
Transcriptome
Proteins
B-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. / Savage, Kerry J.; Monti, Stefano; Kutok, Jeffery L.; Cattoretti, Giorgio; Neuberg, Donna; De Leval, Laurence; Kurtin, Paul; Dal Cin, Paola; Ladd, Christine; Feuerhake, Friedrich; Aguiar, Ricardo C T; Li, Sigui; Salles, Gilles; Berger, Francoise; Jing, Wen; Pinkus, Geraldine S.; Habermann, Thomas Matthew; Dalla-Favera, Riccardo; Harris, Nancy Lee; Aster, Jon C.; Golub, Todd R.; Shipp, Margaret A.

In: Blood, Vol. 102, No. 12, 01.12.2003, p. 3871-3879.

Research output: Contribution to journalArticle

Savage, KJ, Monti, S, Kutok, JL, Cattoretti, G, Neuberg, D, De Leval, L, Kurtin, P, Dal Cin, P, Ladd, C, Feuerhake, F, Aguiar, RCT, Li, S, Salles, G, Berger, F, Jing, W, Pinkus, GS, Habermann, TM, Dalla-Favera, R, Harris, NL, Aster, JC, Golub, TR & Shipp, MA 2003, 'The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma', Blood, vol. 102, no. 12, pp. 3871-3879. https://doi.org/10.1182/blood-2003-06-1841
Savage, Kerry J. ; Monti, Stefano ; Kutok, Jeffery L. ; Cattoretti, Giorgio ; Neuberg, Donna ; De Leval, Laurence ; Kurtin, Paul ; Dal Cin, Paola ; Ladd, Christine ; Feuerhake, Friedrich ; Aguiar, Ricardo C T ; Li, Sigui ; Salles, Gilles ; Berger, Francoise ; Jing, Wen ; Pinkus, Geraldine S. ; Habermann, Thomas Matthew ; Dalla-Favera, Riccardo ; Harris, Nancy Lee ; Aster, Jon C. ; Golub, Todd R. ; Shipp, Margaret A. / The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. In: Blood. 2003 ; Vol. 102, No. 12. pp. 3871-3879.
@article{49dc4eeeb2e34dafafd8b458cff0118a,
title = "The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma",
abstract = "Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in ML-BCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-κB (NF-κB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-κB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.",
author = "Savage, {Kerry J.} and Stefano Monti and Kutok, {Jeffery L.} and Giorgio Cattoretti and Donna Neuberg and {De Leval}, Laurence and Paul Kurtin and {Dal Cin}, Paola and Christine Ladd and Friedrich Feuerhake and Aguiar, {Ricardo C T} and Sigui Li and Gilles Salles and Francoise Berger and Wen Jing and Pinkus, {Geraldine S.} and Habermann, {Thomas Matthew} and Riccardo Dalla-Favera and Harris, {Nancy Lee} and Aster, {Jon C.} and Golub, {Todd R.} and Shipp, {Margaret A.}",
year = "2003",
month = "12",
day = "1",
doi = "10.1182/blood-2003-06-1841",
language = "English (US)",
volume = "102",
pages = "3871--3879",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma

AU - Savage, Kerry J.

AU - Monti, Stefano

AU - Kutok, Jeffery L.

AU - Cattoretti, Giorgio

AU - Neuberg, Donna

AU - De Leval, Laurence

AU - Kurtin, Paul

AU - Dal Cin, Paola

AU - Ladd, Christine

AU - Feuerhake, Friedrich

AU - Aguiar, Ricardo C T

AU - Li, Sigui

AU - Salles, Gilles

AU - Berger, Francoise

AU - Jing, Wen

AU - Pinkus, Geraldine S.

AU - Habermann, Thomas Matthew

AU - Dalla-Favera, Riccardo

AU - Harris, Nancy Lee

AU - Aster, Jon C.

AU - Golub, Todd R.

AU - Shipp, Margaret A.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in ML-BCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-κB (NF-κB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-κB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.

AB - Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in ML-BCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-κB (NF-κB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-κB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.

UR - http://www.scopus.com/inward/record.url?scp=10744228934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744228934&partnerID=8YFLogxK

U2 - 10.1182/blood-2003-06-1841

DO - 10.1182/blood-2003-06-1841

M3 - Article

VL - 102

SP - 3871

EP - 3879

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -