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-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