NF-\u3baB pathways in hematological malignancies

The nuclear factor \u3baB or NF-\u3baB 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-\u3baB is typical of most malignancies and plays a major role in tumorigenesis. In this review, we describe NF-\u3baB 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-\u3baB 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\u2019s lymphoma), T lymphomas (ATLL, ALCL) and multiple myeloma. We describe the interaction of NF-\u3baB 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-\u3baB activity and to induce apoptosis (PARAs and Nutlin-3)