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Background: BCL2-interacting protein 3 (BNIP3) expression varies among cancers, and its role in myeloma cells remains unknown. We investigated the role of BNIP3 overexpression in myeloma cells, and particularly its effects on apoptosis and mitochondria., Methods: A BNIP3-overexpressing plasmid was transfected into the MM.1S and RPMI8226 myeloma cell lines. Transfected cell apoptosis rate and mitochondrial function were determined via flow cytometry and western blotting. We verified the signaling pathway underlying myeloma cell sensitivity to bortezomib (BTZ)., Results: Cell lines carrying the BNIP3-overexpressing plasmid exhibited higher rates of apoptosis and expression of Bax and Cleaved caspase 3 protein than the vector group, and less Bcl-2 protein expression than the control cells. Relative to the vector group, BNIP3-overexpressing strains contained more reactive oxygen species (ROS) and exhibited mitochondrial membrane potential (MMP) and dynamin-related protein 1 (Drp1) upregulation and mitofusin-1 (Mfn1) downregulation. BTZ supplementation increased BNIP3 expression. Relative to the BNIP3-OE group, the BNIP3-OE BTZ-treated group exhibited upregulated Bax and Cleaved caspase 3 protein expression, downregulated Bcl-2 protein expression, higher apoptosis rates, ROS levels, MMP, and Drp1 expression, and lower Mfn1 expression. BTZ treatment induced p38 MAPK (mitogen-activated protein kinase) signaling pathway activation in BNIP3-OE cells. Upon adding N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580, the affected index levels returned to the baseline., Conclusions: BNIP3 overexpression induced apoptosis in myeloma cells and increased myeloma cell sensitivity to BTZ. These effects may be mediated by the ROS/p38 MAPK signaling pathway.

Objective: Antinuclear antibody (ANA)-positive immune thrombocytopenia (ITP) patients have an unsatisfactory prognosis due to the more severe conditions of these patients and poor response to first-line glucocorticoids (GCs). The current study intended to compare the efficacy and safety of AZA plus prednisone and prednisone alone as first-line treatment in ANA-positive ITP patients., Methods: Fifteen ANA-positive ITP patients receiving AZA plus prednisone (AZA + GC group) and eighteen ANA-positive ITP patients receiving prednisone alone (GC group) as first-line treatment were retrospectively enrolled., Results: The complete response (CR) rate (60.0% versus 22.2%) ( P  = 0.038) was increased in the AZA + GC group versus the GC group, while the overall response rate (86.7% versus 55.6%) ( P  = 0.070) only showed an increasing trend that did not achieve statistical significance. In addition, multivariate analysis revealed that AZA + GC (versus GC) (odds ratio = 31.331, P  = 0.018) was independently associated with a higher possibility of achieving CR. Additionally, accumulating relapse-free duration was prolonged in the AZA + GC group versus the GC group (median: 7.8 months versus 3.4 months) ( P  = 0.038). Additionally, the multivariate analysis suggested that AZA + GC (versus GC) (hazard ratio = 0.306, P  = 0.007) was independently correlated with longer accumulating relapse-free duration. The incidence of adverse events did not differ between the two groups (all P  > 0.05), and the common adverse events in the AZA + GC group were pneumonia (13.3%), anemia (13.3%), cough (13.3%), nausea (6.7%), and granulocytopenia (6.7%), which were all tolerable and manageable., Conclusion: First-line AZA plus prednisone realizes a better hematological response and relapse-free duration with acceptable adverse events compared to prednisone alone in ANA-positive ITP patients.