The Whole Blood Transcriptomic Analysis in Sickle Cell Disease Reveals RUNX3 as a Potential Marker for Vaso-Occlusive...

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Sickle cell disease (SCD) is a common inherited blood disorder characterized by painful vaso-occlusive crises (VOC) and organ damage.
• Significant variability in SCD presentation complicates outcome prediction.
• Understanding gene expression profiles in SCD is crucial for identifying disease mechanisms and potential biomarkers.

Purpose of the Study:

• To characterize whole blood gene expression in Bahraini SCD patients during steady-state and VOC.
• To identify differentially expressed genes and pathways associated with SCD.
• To investigate the role of transcription factor RUNX3 as a potential biomarker for VOC.

Main Methods:

• Whole blood gene expression profiling using microarrays and quantitative PCR.
• Comparison of gene expression between SCD patients (steady-state and VOC) and healthy controls.
• Gene Ontology (GO) enrichment analysis to identify deregulated pathways.
• Protein concentration measurement of RUNX3 using ELISA.

Main Results:

• Significant dysregulation of 2073 genes in steady-state SCD and 3363 genes in VOC compared to controls.
• 1078 genes were differentially expressed between VOC and steady-state SCD.
• Immune and hematopoietic pathways were significantly deregulated.
• RUNX3 was significantly down-regulated in VOC, with reduced protein levels observed during crises.

Conclusions:

• Gene expression profiling reveals significant molecular alterations in SCD, particularly during VOC.
• RUNX3 down-regulation during VOC suggests its potential as a predictive biomarker for sickle cell crises.
• Further research is warranted to validate RUNX3's clinical utility in SCD management.