The following is a summary of “Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease,” published in the January 2024 issue of Oncology by Yin et al.
Myelodysplastic syndrome (MDS) originates from pathogenic bone marrow mesenchymal stem cells (MSC) interacting with hematopoietic stem cells (HSC). However, the considerable heterogeneity among MDS patients poses challenges in identifying common targets, particularly in studies with limited sample sizes.
This investigation aims to elucidate sequential molecular changes and pinpoint biomarkers within MSC during the transformation of MDS. Investigators conducted a comprehensive analysis using multidimensional data from three publicly available microarray and TCGA datasets. Additionally, MDS-MSC was isolated and cultured in vitro to assess the identified biomarkers’ diagnostic and prognostic potential. Their findings revealed a greater molecular homogeneity in normal MSCs compared to MDS-MSC. Enrichment analysis indicated involvement in biological processes such as embryonic skeletal system morphogenesis and angiogenesis, along with pathways related to p53 and MAPK signaling, as evidenced by differential gene expression. Notably, the researchers identified HOXB3 and HOXB7 as potential causative genes that exhibited gradual upregulation during the transition from normal to MDS and subsequently to AML.
Furthermore, inhibition of HOXB3 and HOXB7 in MSCs demonstrated enhanced cell proliferation and differentiation, inhibition of cell apoptosis, and restoration of functions supporting hematopoietic differentiation in HSCs. In conclusion, their extensive gene expression profiling in MSCs during MDS has unveiled dysregulated genes and biological processes.
Notably, HOXB3 and HOXB7 emerge as promising novel surrogate targets for therapeutic interventions and diagnostic applications in MDS. This study contributes to a deeper understanding of MDS at the molecular level. It offers potential avenues for targeted therapeutic strategies and precision diagnostics in managing this complex hematologic disorder.
Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11859-w