title: NF-κB pathways in hematological malignancies.
abstract: The nuclear factor κB or NF-κB transcription factor family plays a key role in several cellular functions, i.e. inflammation, apoptosis, cell survival, proliferation, angiogenesis, and innate and acquired immunity. The constitutive activation of NF-κB is typical of most malignancies and plays a major role in tumorigenesis. In this review, we describe NF-κB and its two pathways: the canonical pathway (RelA/p50) and the non-canonical pathway (RelB/p50 or RelB/p52). We then consider the role of the NF-κB subunits in the development and functional activity of B cells, T cells, macrophages and dendritic cells, which are the targets of hematological malignancies. The relevance of the two pathways is described in normal B and T cells and in hematological malignancies, acute and chronic leukemias (ALL, AML, CLL, CML), B lymphomas (DLBCLs, Hodgkin's lymphoma), T lymphomas (ATLL, ALCL) and multiple myeloma. We describe the interaction of NF-κB with the apoptotic pathways induced by TRAIL and the transcription factor p53. Finally, we discuss therapeutic anti-tumoral approaches as mono-therapies or combination therapies aimed to block NF-κB activity and to induce apoptosis (PARAs and Nutlin-3).
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy, chiara.gasparini@burlo.trieste.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gasparini
authors.forename: Claudio
authors.initials: C
authors.lastname: Celeghini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monasta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D016328:NF-kappa B; D010879:Piperazines; C498143:RELA protein, human; C497593:RELB protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D051841:Transcription Factor RelB; C482205:nutlin 3