We tested the role of bcl-2 by transfecting 2 low bcl-2-expressing myeloma cell lines, ARP-1 and 8226, with a bcl-2 expression vector and compared the effects of DEX and MEL on apoptosis, cell cycle distribution and the levels of proapoptotic (bax) and antiapoptotic (bcl-2, bclx) proteins.
Moreover, miR-324-5p potentiated the anti-MM efficacy of bortezomib through regulating the activities of multidrug-resistance proteins and the expression of Bcl-2 family genes.
Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone.
Ex vivo pharmacodynamic analyses demonstrated that the combination of JQ1 and ricolinostat led to significantly lower MM cell proliferation and increased apoptosis and diminished expression of c-MYC and BCL-2.
CD34(+) cells were resistant to Ad-p53-mediated apoptosis, and CFU-GM and BFU-E colony formation was not affected by treatment with Ad-p53.Ad-p53 is a potent inducer of apoptosis in MM cell lines and in freshly isolated myeloma cells expressing low levels of bcl-2.
Replication deficient Ad-p53 and human recombinant Apo2L/TRAIL were used.Myeloma cells with mutated/w.t. p53 and varying expression of bcl-2 were used to test the effect of Ad-p53, Apo2L/TRAIL, or both, on apoptosis, measured by annexin V.
To conclude, we suggest that the expression pattern of the Bcl-2 family of proteins separates the malignant phenotype of MM from normal plasma cells, and that the protecting effect of IL-6 may be conducted via an altered balance between these proteins.
ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL.
Approximately, 20% of myeloma patients will exhibit <i>t</i> (11;14) associated with high BCL-2 expression making venetoclax an attractive therapeutic option.
Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.
Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course.
Forced expression of bcl-2 in 8226 and ARP-1 multiple myeloma (MM) cell lines expressing relatively low levels of bcl-2, resulted in 1-2 log increase in resistance to dexamethasone (DEX)-induced apoptosis.
It is at present unclear whether the high expression of bcl-2 in human myeloma is the result of a deregulated expression associated with the malignant phenotype or a mere reflection of the bcl-2 expression typical of normal plasma cells.