BCL2L13 protein prevents apoptosis in acute myeloid leukemia cells

Abstract

Abstract Objectives The B cell lymphoma-2 (BCL-2) protein group is essential for regulating apoptosis. BCL2L13 harbors all BH domains present in the BCL-2 protein family in addition to a BHNo domain comprising 250 amino acids at its C-terminal. BCL2L13 is highly expressed in AML and is involved in apoptosis. We investigated the possibility of discovering BCL2L13 as a treatment target for acute leukemia. Methods We reduced the expression of BCL2L13 in Mono Mac 6 (MM6) cells using shRNA and overexpressed BCL2L13 in THP-1 cells. MM6 and THP-1 cells were treated with staurosporine (STS) to confirm the role of BCL2L13 in apoptosis. Results In acute myeloid leukemia (AML) cells, BCL2L13 is involved in inhibiting apoptosis as evidenced by its strikingly augmented expression in these cells. BCL-2 was downregulated and cleaved Caspase 3, and sphingosine-1-phosphate phosphatase 1 (SGPP1) was upregulated when MM6 cells with knockdown BCL2L13 were treated with STS, which significantly increased their apoptosis. Furthermore, mitochondrial membrane potential decreased in MM6 cells in response to the downregulation of BCL2L13. In BCL2L13-depleted MM6 cells, the amount of cytochrome c increased in the cytoplasm. The THP-1 cells overexpressing BCL2L13 and treated with STS showed a significant decrease in the expression of genes related to apoptosis induction, resulting in decreased apoptosis. Conclusion BCL2L13 inhibits apoptosis in AML, and BCL2L13-specific inhibition might serve as a new strategy for treating this condition.