A study presented at the Society of Hematologic Oncology 2024 Annual Meeting highlighted the significant overexpression of the SLC40A1 gene in acute myeloid leukemia (AML) and its association with poor prognosis.
“Ferroportin, encoded by the SLC40A1 gene, is vital for cellular iron export, but its significance and interactions in AML are unclear,” the researchers wrote.
To investigate this, researchers analyzed SLC40A1 gene expression in AML samples (n=173) and control samples (n=70). The researchers utilized the Linked Omics database to examine correlations between SLC40A1 and other genes, assessed prognostic significance using Kaplan–Meier survival curves, and explored DNA methylation patterns through the MEXPRESS database. Gene set enrichment analysis (GSEA) was performed to elucidate the molecular mechanisms associated with SLC40A1, and its relationship with immune checkpoints was analyzed with the SANGER Box 3.0 database.
Following the analysis, researchers reported that SLC40A1 mRNA levels were significantly higher in AML patients compared with controls and were associated with poorer overall survival (P<0.05). The study identified positive correlations between SLC40A1 and genes such as DNAJC6, CD59, PLS1, GCLM, and CAPRIN2, whereas negative correlations were observed with genes such as MSLN, MYH11, DAGLB, ST18, and PLCD3.
Additionally, lower levels of DNA methylation of SLC40A1 were observed in AML, which was inversely related to its gene expression. GSEA showed that SLC40A1 is involved in biological processes such as lymphocyte homeostasis, endothelium development, spleen development, cell communication, and differentiation. Its molecular functions include iron ion transmembrane transport, metal cluster binding, growth factor binding, and catalytic activity. Pathway analysis showed that SLC40A1 was implicated in several critical pathways, including hematopoietic stem cell differentiation, ferroptosis, mRNA surveillance, autophagy, TGF-beta signaling, and stem cell pluripotency.
Furthermore, SLC40A1 was positively correlated with immune checkpoints such as CD160, CD274, CD40, CD44, and CD80, suggesting a potential role in modulating immune responses in AML.
“This study provides insights into the molecular mechanisms underlying SLC40A1 involvement in AML pathogenesis, offering avenues for novel therapeutic interventions,” the researchers concluded.
Reference
Goel H, Chopra A, Ranjan A, et al. A prospective study to evaluate the prognostic implications and molecular mechanism of SLC40A1 gene in primary acute myeloid leukemia. Abstract #AML-013. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.