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Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large cell, and other peripheral T-cell lymphomas

Official URL:https://doi.org/10.1182/blood-2004-09-3620
PubMed:View item in PubMed
Creators Name:Mathas, S. and Joehrens, K. and Joos, S. and Lietz, A. and Hummel, F. and Janz, M. and Jundt, F. and Anagnostopoulos, I. and Bommert, K. and Lichter, P. and Stein, H. and Scheidereit, C. and Doerken, B.
Journal Title:Blood
Journal Abbreviation:Blood
Page Range:4287-4293
Date:25 August 2005
Keywords:Cell Line, Dimerization, Hodgkin Disease, I-kappa B Proteins, Interleukin-9, Microarray Analysis, NF-kappa B p50 Subunit, Neoplastic Gene Expression Regulation, Oncogene Proteins v-rel, Peripheral T-Cell Lymphoma, Protein Binding, Proto-Oncogene Proteins, Transcription Factors
Abstract:Transcription factor nuclear factor kappa B (NF-κB) 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-κB system has not been equivalently investigated. Here we describe constitutive NF-κB p50 homodimer [(p50) 2] activity in ALCL cells in the absence of constitutive activation of the IκB kinase (IKK) complex. Furthermore, (p50) 2 contributes to the NF-κB 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
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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