Susceptibility of multiple myeloma to B-cell lymphoma 2 family inhibitors

Multiple myeloma (MM) is a biologically complex hematological disorder defined by the clonal proliferation of malignant plasma cells producing excessive monoclonal immunoglobulin that interacts with components of the bone marrow microenvironment, resulting in the major clinical features of MM. Despite the development of numerous protocols to treat MM patients, this cancer remains currently incurable; due in part to the emergence of resistant clones, highlighting the unmet need for innovative therapeutic approaches. Accumulating evidence suggests that the survival of MM molecular subgroups depends on the expression profiles of specific subsets of anti-apoptotic B-cell lymphoma (BCL)-2 family members. This review summarizes the mechanisms underlying the anti-myeloma activities of the potent BCL-2 family protein inhibitors, individually or in combination with conventional therapeutic options, and provides an overview of the strong rationale to clinically investigate such interventions for MM therapy.