Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas.
Transcription factor nuclear factor kappa B (NF-kappaB) plays a central role in the pathogenesis of classical Hodgkin lymphoma (cHL). In anaplastic large-cell lymphomas (ALCLs), which share molecular lesions with cHL, the NF-kappaB system has not been equivalently investigated. Here we describe constitutive NF-kappaB p50 homodimer [(p50)2] activity in ALCL cells in the absence of constitutive activation of the IkappaB kinase (IKK) complex. Furthermore, (p50)2 contributes to the NF-kappaB activity in Hodgkin/Reed-Sternberg (HRS) cells. Bcl-3, which is an inducer of nuclear (p50)2 and is associated with (p50)2 in ALCL and HRS cell lines, is abundantly expressed in ALCL and HRS cells. Notably, a selective overexpression of Bcl-3 target genes is found in ALCL cells. By immunohistochemical screening of 288 lymphoma cases, a strong Bcl-3 expression in cHL and in peripheral T-cell non-Hodgkin lymphoma (T-NHL) including ALCL was found. In 3 of 6 HRS cell lines and 25% of primary ALCL, a copy number increase of the BCL3 gene locus was identified. Together, these data suggest that elevated Bcl-3 expression has an important function in cHL and peripheral T-NHL, in particular ALCL.
Mathas
Stephan
S
Max-Delbrück-Center for Molecular Medicine, FG Dörken, D-13125 Berlin, Germany. mathas@rrk-berlin.de
Jöhrens
Korinna
K
Joos
Stefan
S
Lietz
Andreas
A
Hummel
Franziska
F
Janz
Martin
M
Jundt
Franziska
F
Anagnostopoulos
Ioannis
I
Bommert
Kurt
K
Lichter
Peter
P
Stein
Harald
H
Scheidereit
Claus
C
Dörken
Bernd
B
D000081242:B-Cell Lymphoma 3 Protein; D002460:Cell Line; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D046228:Microarray Analysis; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D020572:Oncogene Proteins v-rel / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D020672:I-kappa B Proteins; D016906:Interleukin-9; D052002:NF-kappa B p50 Subunit; D020572:Oncogene Proteins v-rel; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors