Altered Expression of Epigenetic Modifiers Identifies Novel Biomarkers and Therapeutic Targets in AL Amyloidosis

Background: Immunoglobulin light chain amyloidosis (ALA) is a plasma cell dyscrasia characterized by the accumulation of amyloid fibrils formed by clonal plasma cells (PC) in the bone marrow (BM). While MM (multiple myeloma) is present at the time of diagnosis in 10% of ALA patients, nearly 30% of MM patients have subclinical amyloid deposits in the BM and/or in vital organs. Differential diagnoses of ALA, monoclonal gammopathy of undetermined significance (MGUS), and MM are challenging because these malignancies share genetic similarities. Unrecognized ALA can be life-threatening due to the side effects of some MM treatment regimens. Thus, identification of epigenetic alterations detected at the transcriptome level selectively associated with ALA is needed to improve patient outcomes.