Long Circulating RNAs Packaged in Extracellular Vesicles: Prospects for Improved Risk Assessment in Childhood B-Cell...

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Bone marrow biopsies are invasive for diagnosing and monitoring childhood B-cell acute lymphoblastic leukemia (B-ALL).
• Small extracellular vesicles (sEVs) in blood contain RNA biomarkers, offering a less invasive liquid biopsy approach.
• Longer RNA species (mRNAs, lncRNAs, circRNAs) in EVs are underexplored for B-ALL risk stratification.

Purpose of the Study:

• To characterize the long RNA transcriptome within blood-derived sEVs from childhood B-ALL patients.
• To identify potential RNA biomarkers in sEVs for molecular subtyping and risk stratification of B-ALL.
• To establish a non-invasive method for B-ALL diagnosis and monitoring.

Main Methods:

• Immuno-purification of sEVs from peripheral blood of B-ALL patients and cell models.
• Whole-transcriptome sequencing targeting RNA transcripts longer than 200 nucleotides.
• Development of a novel data analysis pipeline for identifying RNA species in sEVs.

Main Results:

• Identified 102 distinct RNA transcripts (mRNAs, lncRNAs, circRNAs, pseudogenes) in patient-derived sEVs.
• Detected specific RNA profiles associated with two molecular subgroups of B-ALL.
• Demonstrated the potential of these transcripts as biomarkers for risk-based stratification at diagnosis.

Conclusions:

• Circulating long RNA transcripts in blood-derived sEVs represent a novel, non-invasive biomarker source for childhood B-ALL.
• This approach can aid in risk stratification and potentially replace invasive bone marrow biopsies.
• Highlights the potential of liquid biopsies for personalized B-ALL management.