Extracellular Vesicles in B Cell Acute Lymphoblastic Leukemia
Monday, Oct. 17, 1-2 p.m.
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B-cell acute lymphoblastic leukemia (B-ALL) is a blood cancer that begins in the bone marrow (BM), with immature B lymphoblasts accumulating and out crowding other cells and subsequently infiltrating peripheral blood (PB) and the central nervous system (CNS). B-ALL is one of the most prevalent pediatric cancers, with a cure rate of about 90%, which reduces to 30-50% upon relapse. A key prognosticator of B-ALL relapse is measurable residual disease (MRD), where lymphoblasts that evade the cytotoxic effects of chemotherapy persist in the BM and CNS. Current methods for monitoring MRD are invasive, laborious and can only be done infrequently. Thus, new methods are needed that allow clinicians to monitor MRD closely. For this, we hypothesize that extracellular vesicles (EVs) – lipid membrane-bound nanoparticles that carry bioactive cargo could potentially be used for less invasive and real-time monitoring of MRD. To test this hypothesis, we identified and validated three pediatric B-ALL cell lines, CCRF-SB, RCH-ACV and UoC-B1, as study models. We characterized pediatric B-ALL EV characteristics, including their shape, size, and concentration. Subsequently, we investigated a clinically amenable EV isolation technique by comparing peptide-affinity, polyethylene glycol, and size exclusion chromatography-based methods. Next, we analyzed the size, concentration, and nucleic acid cargo of non-cancer donor (NCD) and B-ALL blood plasma EVs. We found the peptide-affinity method as the most clinically amenable in our hands. Also, B-ALL plasma contains more EVs than NCD, with an enrichment of 30-160 nm EVs. Finally, we found a signature of EV RNA cargo containing miRNAs, lncRNAs and mRNAs that differentiates B-ALL from HD. This signature is a bedrock that will allow further exploration of the potential of EV cargo for MRD monitoring.
Presented by Department of Biochemistry