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NF-κB pathways in hematological malignancies

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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).

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Acknowledgments

We thank Dr. Fabio Rosso for the artwork of this review.

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  1. Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Via dell’Istria 65/1, 34137, Trieste, Italy

    Chiara Gasparini, Lorenzo Monasta & Giorgio Zauli

  2. Department of Life Sciences, University of Trieste, Trieste, Italy

    Claudio Celeghini

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  1. Chiara Gasparini
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Gasparini, C., Celeghini, C., Monasta, L. et al. NF-κB pathways in hematological malignancies. Cell. Mol. Life Sci. 71, 2083–2102 (2014). https://doi.org/10.1007/s00018-013-1545-4

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