Multiple myeloma with amplification of chromosome 1q is highly sensitive to MCL-1 targeting

Abstract

Pro-survival BCL-2 family proteins are potent inhibitors of apoptosis and are often overexpressed in lymphoid malignancies. In multiple myeloma (MM), BCL-2 inhibitor Venetoclax induces cell death, particularly in presence of t(11;14) and high BCL-2 expression. The most prominent BCL-2 family member in MM is MCL-1, whose expression contributes to survival of malignant plasma cells and overexpression correlates with poor prognosis. Amplification of 1q21, the chromosome region that contains the MCL1 locus, occurs in approximately 40% of newly diagnosed MM, and 70% at relapse.