Oblimersen was the first drug to demonstrate proof-of-principle specific down-regulation of BCL-2 protein in human tumors (156, 157) and provided initial preclinical and clinical evidence of synergy with cytotoxic drugs, biological agents, and steroids in a variety of human cancers, including non-Hodgkin lymphoma, multiple myeloma and acute myeloid leukemia (AML) (156–159). This evidence concerns the gene BCL2 and plasma cell myeloma.