Multiple myeloma (MM) currently accounts for less than 1% of total cancer occurrence worldwide. Despite decades of research and design of therapeutics, clinical responses to molecular-targeted drugs tend to vary and are often unsuccessful. This hematological malignancy originates in the plasma cells involved in immune response. Evasion of apoptosis is a hallmark of cancer malignancy in MM. Induction of apoptosis is regulated by the sequestering of pro-apoptotic BH3-only proteins by anti-apoptotic BCL-2 family members. Bim, a pro-apoptotic BH3-only protein, has emerged as a key contributor to the activation of apoptosis in MM. Little, however, is known about its role in response to Mcl-1 and Bcl-2 based therapeutics and contribution to resistance. Our laboratory has generated cell lines with complete knockout of Bim and BimEL, the most abundant isoform of Bim. In this study, we seek to elucidate the role of Bim in apoptosis in response to therapeutics for MM. Furthermore, we seek to understand the specific resistance mechanisms involved in MM through the elucidation of the Bim interactome. These findings will provide a better understanding of the induction of apoptosis in the absence of Bim, leading to the design of more precise therapeutics for MM.
