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).
MeSH terms
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Antineoplastic Agents / therapeutic use
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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B-Lymphocytes / pathology
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Carcinogenesis / genetics
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Gene Expression Regulation, Neoplastic*
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Hematologic Neoplasms / drug therapy
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Hematologic Neoplasms / genetics*
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Hematologic Neoplasms / metabolism
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Hematologic Neoplasms / pathology
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Humans
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Imidazoles / therapeutic use
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Macrophages / drug effects
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Macrophages / metabolism
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Macrophages / pathology
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NF-kappa B / genetics*
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NF-kappa B / metabolism
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Piperazines / therapeutic use
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Signal Transduction*
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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TNF-Related Apoptosis-Inducing Ligand / genetics
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TNF-Related Apoptosis-Inducing Ligand / metabolism
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Transcription Factor RelA / genetics*
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Transcription Factor RelA / metabolism
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Transcription Factor RelB / genetics*
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Transcription Factor RelB / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antineoplastic Agents
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Imidazoles
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NF-kappa B
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Piperazines
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RELA protein, human
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RELB protein, human
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Transcription Factor RelA
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Tumor Suppressor Protein p53
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Transcription Factor RelB
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nutlin 3