Arsenic Sulfide Induces Apoptosis in Myelodysplastic Neoplasm Cells Through the Suppression of ABI2

硫化砷通过抑制ABI2诱导骨髓增生异常肿瘤细胞凋亡

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Abstract

BACKGROUND: Myelodysplastic neoplasms (MDS) are a category of myeloid malignancies that can progress to acute myeloid leukemia (AML). Arsenic sulfide (As₂S₂) has demonstrated efficacy in the treatment of MDS. However, further investigation is required to elucidate its specific therapeutic targets. OBJECTIVE: To examine the influence of ABI2 on MDS and clarify the regulatory role of As₂S₂ on ABI2 within the therapeutic framework of MDS. METHODS: To explore ABI2's role in the expression and prognosis of patients with hematological malignancies, RNA interference was used to reduce ABI2 expression in SKM-1, K562 and MDS-L cell lines. The therapeutic efficacy of As₂S₂ and its regulatory impact on ABI2 were evaluated both in vitro and in vivo. RESULTS: ABI2 was found to be overexpressed in the peripheral blood of patients with MDS and AML, which was significantly associated with decreased survival rates in AML patients. Inhibition of ABI2 decreased the proliferation and increased the apoptosis of SKM-1, K562 and MDS-L cells. As₂S₂ also inhibited cell proliferation and induced apoptosis in these cells, but its efficacy diminished significantly with ABI2 silencing. Additionally, As₂S₂ showed therapeutic benefits in NHD13 mice by downregulating bone marrow ABI2 expression. CONCLUSION: The collective findings suggest that ABI2 is significantly overexpressed in MDS and AML, and its expression was correlated with unfavorable prognostic outcomes. Furthermore, As₂S₂ demonstrates therapeutic efficacy in MDS by modulating the expression levels of ABI2.

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