Potential role of PDLIM1 in the tumorigenesis of acute myeloid leukemia: a comprehensive bioinformatics and in vitro study

PDLIM1 has been associated with the development of multiple malignancies, but its expression profile and clinical relevance in acute myeloid leukemia (AML) have not been fully characterized. In this study, publicly available datasets were analyzed to assess differences in PDLIM1 mRNA expression between AML samples and healthy controls, while its protein abundance was preliminarily examined by immunohistochemistry. CCK8 and Transwell assays were used to evaluate the effects of PDLIM1 on the proliferation, invasion, and migration of AML cells. The molecular functions of PDLIM1 were investigated using an integrated multi-omics framework that included weighted gene co-expression network analysis (WGCNA), machine learning, single-cell RNA sequencing, immune cell infiltration assessment, and functional enrichment analysis. Molecular docking was also performed with AutoDock Vina to estimate the binding affinities of PDLIM1 for candidate compounds, and the highest-ranking binding conformations were visualized using PyMOL. PDLIM1 was markedly upregulated in AML tissues compared with healthy control tissues, with a standardized mean difference of 0.91 (95% CI, 0.53–1.29). This result was preliminarily validated by immunohistochemistry (IHC) staining. Clinicopathological analysis indicated that elevated PDLIM1 expression was associated with greater proportions of blasts in the bone marrow and peripheral blood, as well as increased peripheral white blood cell counts. CCK8 and Transwell assays revealed that overexpression of PDLIM1 significantly enhanced the proliferation, invasion, and migration abilities of AML cells. Single-cell transcriptomic analysis demonstrated that PDLIM1 was primarily enriched in leukemia stem cell (LSC) and AML cell populations, indicating that it may serve as a molecular marker for LSCs. WGCNA identified 332 genes related to PDLIM1 expression. Kyoto Encyclopedia of Genes and Genomes analysis further revealed significant enrichment of these genes in several biological pathways, including focal adhesion. Potential small-molecule agents associated with PDLIM1 expression were subsequently screened through the Gene Set Cancer Analysis database. The highest-ranked compounds were A-770041, afatinib, WZ-1-84, dasatinib, erlotinib, gefitinib, saracatinib, and WH-4-023. Among these compounds, A-770041 exhibited the lowest predicted binding energy, and local docking visualization identified multiple intermolecular interactions at favorable distances, suggesting that it may be the most promising candidate ligand among those evaluated. Collectively, these findings indicate that PDLIM1 is markedly upregulated in AML and LSCs and may represent a potential therapeutic target.