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
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.
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U2 - 10.1182/blood-2003-06-1841
DO - 10.1182/blood-2003-06-1841
M3 - Article
C2 - 12933571
AN - SCOPUS:10744228934
SN - 0006-4971
VL - 102
SP - 3871
EP - 3879
JO - Blood
JF - Blood
IS - 12
ER -