Luks-PV induce HOXA9 degradation through autophagy in Acute myeloid leukemia with HOXA9 overexpression

Abstract Background: Our previous studies have demonstrated that Luks-PV have good anti-leukemia ability effects and could possibly be a promising therapy for adult acute myeloid leukemia (AML). Aberrant over-expression of HOXA9 is a prominent feature of AML driven by multiple oncogenes, and therapeutic degrading of HOXA9 may be an effective treatment strategy in AML. This paper focused on the Luks-PV-regulating autophagy pathway, aiming to investigate the role of Luks-PV in mixed-lineage leukemia (MLL)-rearranged AML. Methods: The data of leukemia patients were downloaded from the gene expression profiling of TCGA datasets. Taking primary AML and THP-1 cells as the model system in vitro, Luks-PV-inhibited cell proliferation was determined by CCK‐8 and flow cytometry assays. The role of Luks-PV in autophagy regulation was analyzed using immunoblotting, transfection and immunofluorescence.Results: HOXA9 was over-expressed and associated with a poor prognosis in AML patients bearing MLL rearrangement. After the application of pharmacologic inhibitors of autophagy, Luks-PV induced cytotoxic autophagy in AML cells, as suggested by biochemical and microscopy results. HOXA9 molecules were detectable within autophagosomes after Luks-PV treatment, indicating that autophagy induction accounted for the degradation of HOXA9. Moreover, Luks-PV-induced HOXA9 downregulation inhibited AML cell proliferation, suggesting that HOXA9 could be degraded through Luks-PV-induced autophagy.Conclusion: Luks-PV suppresses AML cell proliferation by inducing HOXA9 degradation.