Amyloidosis: Systems-Based Therapies

In this chapter, the authors will discuss the epidemiology and clinical presentations of amyloidosis. The main body of this chapter will concentrate on treatment options, both FDA-approved and experimental, specific to the various forms of amyloidosis. Since this set of diseases can affect multiple organ systems, we tackle the therapeutic avenues and the current challenges in each system under clinical investigation, including neurological, psychiatric, gastrointestinal, cardiovascular, endocrine, renal and hematologic, in addition to options for palliative treatment for severe symptom management and improved quality of life. Several recent groundbreaking discoveries have opened up the potential for successful treatment of peripheral and central neurological amyloidoses making this an exciting and evolving field

RELT Stains Prominently in B-cell Lymphomas and Binds the Hematopoietic Transcription Factor MDFIC

Receptor Expressed in Lymphoid Tissues (RELT) is a human tumor necrosis factor receptor superfamily member (TNFRSF) that is expressed most prominently in cells and tissues of the hematopoietic system. RELL1 and RELL2 are two homologs that physically interact with RELT and co-localize with RELT at the plasma membrane. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members. The transcription factor MyoD family inhibitor domain-containing (MDFIC) was identified in a yeast two-hybrid genetic screen using RELL1 as bait. MDFIC co-localizes with RELT family members at the plasma membrane; this co-localization was most prominently observed with RELL1 and RELL2. In vitro co-immunoprecipitation (Co-IP) was utilized to demonstrate that MDFIC physically interacts with RELT, RELL1, and RELL2. Co-IP using deletion mutants of MDFIC and RELT identified regions important for physical association between MDFIC and RELT family members and a computational analysis revealed that RELT family members are highly disordered proteins. Immunohistochemistry of normal human lymph nodes revealed RELT staining that was most prominent in macrophages. Interestingly, the level of RELT staining significantly increased progressively in low and high-grade B-cell lymphomas versus normal lymph nodes. RELT co-staining with CD20 was observed in B-cell lymphomas, indicating that RELT is expressed in malignant B cells. Collectively, these results further our understanding of RELT-associated signaling pathways, the protein structure of RELT family members, and provide preliminary evidence indicating an association of RELT with B-cell lymphomas