IMPACT OF NAD+ SYNTHESIS ENZYMES ON MULTIPLE MYELOMA PATIENT OUTCOMES AND ONGOING INVESTIGATION OF MECHANISMS OF FAMILIAL CLUSTERING OF MULTIPLE MYELOMA IN NOVA SCOTIA

Abstract

Multiple myeloma (MM) is an incurable plasma cell neoplasm, which makes it ideal for novel therapeutic targets such as Nicotinamide Dinucleotide (NAD+). NAD+ is synthesized through one of three pathways: catalyzed by NAMPT, NAPRT, or IDO. We compared the expression of these rate-limiting enzymes in NAD+ synthesis against patient outcomes to investigate their feasibility as prognostic biomarkers in MM using OPAL multiplex immunohistochemistry. There was significant increase in NAMPT expression intensity in MM cases compared to control cases. NAPRT and NAMPT co-expressed in MM predicted worse patient survival compared to NAMPT expression alone. Increased NAPRT expression intensity correlated with shorter overall survival. Targeting these two pathways in concert could offer novel therapeutic opportunities for improving MM patient outcomes. We also include our preliminary work on the genetic and environmental causes of familial clustering of MM observed in Nova Scotia.