RPPH1 promotes the progression of High-Risk acute myeloid leukemia through NF-κB signaling and Th17 expression.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a poor prognosis, thus necessitating novel prognostic biomarkers and therapeutic targets. This study investigated the role of long non-coding RNAs (lncRNAs) in the pathogenesis and risk stratification of AML. Transcriptome sequencing was conducted on bone marrow samples from 20 patients with AML (10 low/intermediate-risk and 10 high-risk), revealing 344 differentially expressed lncRNAs and 1,109 dysregulated mRNAs. The application of functional enrichment analysis revealed that NF-κB signaling activation and Th17 cell differentiation represent the key pathways associated with high-risk AML. Among dysregulated lncRNAs, RNase P RNA Component H1 (RPPH1) demonstrated significant upregulation in patients with high-risk AML, thus establishing it as a promising candidate for further investigation. Functional validation employing AML cell lines MV-4-11 and MOLM13 demonstrated that RPPH1 overexpression enhanced cell proliferation and suppressed apoptosis, whereas its knockdown resulted in opposite effects. Mechanistically, RPPH1 enhanced NF-κB p65 phosphorylation and upregulated IL-17 A expression, thereby activating downstream oncogenic targets, including PLAC8, LRP12, and CRABP2. The present findings suggest that RPPH1 regulates AML progression via the NF-κB/Th17A signaling axis, providing new insights into its role in disease pathogenesis and immune microenvironment remodeling. In view of its prognostic and therapeutic potential, RPPH1 can function as both a biomarker and a promising therapeutic target for high-risk AML.