IDENTIFY FUNCTIONAL PROTEINS INTERACTING WITH MMSET IN MULTIPLE MYELOMA

Abstract

Recurrent chromosomal translocations are central to the pathogenesis of MM, with t(4;14) being the second-most common and associated with poor prognosis. NSD2 is overexpressed as a result of the t(4;14) translocation and has been suggested to be the primary oncogenic factor in t(4;14)+ MM. To address the relevant pathways that contributed to myelomagenesis, SILAC-based mass-spectrometry analysis was used to determine NSD2-interacting proteins. We identified 74 proteins and in silico analysis showed that one of them, SMARCA2, interacts with NSD2. Comparison of SMARCA2 expression across MM cell lines with different translocation statuses showed that SMARCA2 was highly expressed in t(4;14)+ MM cells but not in t(4;14)- MM cells. SMARCA2 KD in t(4;14)+ MM cells showed reduced cell growth and capacity to form colonies. We further investigated how NSD2 and SMARCA2 regulate the expressions of key myeloma genes, such as PRL3 and CCND1.