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Biomedicines 2018, 6(2), 38; https://doi.org/10.3390/biomedicines6020038

NF-κB Activation in Lymphoid Malignancies: Genetics, Signaling, and Targeted Therapy

Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Hoppe-Seyler-Str. 4, 72076 Tuebingen, Germany
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Received: 5 March 2018 / Revised: 20 March 2018 / Accepted: 22 March 2018 / Published: 26 March 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
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Abstract

The NF-κB transcription factor family plays a crucial role in lymphocyte proliferation and survival. Consequently, aberrant NF-κB activation has been described in a variety of lymphoid malignancies, including diffuse large B-cell lymphoma, Hodgkin lymphoma, and adult T-cell leukemia. Several factors, such as persistent infections (e.g., with Helicobacter pylori), the pro-inflammatory microenvironment of the cancer, self-reactive immune receptors as well as genetic lesions altering the function of key signaling effectors, contribute to constitutive NF-κB activity in these malignancies. In this review, we will discuss the molecular consequences of recurrent genetic lesions affecting key regulators of NF-κB signaling. We will particularly focus on the oncogenic mechanisms by which these alterations drive deregulated NF-κB activity and thus promote the growth and survival of the malignant cells. As the concept of a targeted therapy based on the mutational status of the malignancy has been supported by several recent preclinical and clinical studies, further insight in the function of NF-κB modulators and in the molecular mechanisms governing aberrant NF-κB activation observed in lymphoid malignancies might lead to the development of additional treatment strategies and thus improve lymphoma therapy. View Full-Text
Keywords: NF-κB; lymphoma; leukemia; CARMA1; CARD11; CD79; MyD88 NF-κB; lymphoma; leukemia; CARMA1; CARD11; CD79; MyD88
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Grondona, P.; Bucher, P.; Schulze-Osthoff, K.; Hailfinger, S.; Schmitt, A. NF-κB Activation in Lymphoid Malignancies: Genetics, Signaling, and Targeted Therapy. Biomedicines 2018, 6, 38.

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