NF-kappa B pathways in hematological malignancies

作者：Gasparini Chiara^*; Celeghini Claudio; Monasta Lorenzo; Zauli Giorgio

来源：Cellular and Molecular Life Sciences, 2014, 71(11): 2083-2102.

DOI：10.1007/s00018-013-1545-4

• Hematologic neoplasms
• NF-kappa B
• RelB
• RelA
• TNF-related apoptosis-inducing ligand
• p53

The nuclear factor kappa B or NF-kappa B 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-kappa B is typical of most malignancies and plays a major role in tumorigenesis. In this review, we describe NF-kappa B 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-kappa B 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-kappa B 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-kappa B activity and to induce apoptosis (PARAs and Nutlin-3).

• 出版日期2014-6