RESUMEN
Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative cell cycle regulation, potentially suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. This signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.
RESUMEN
Extracellular vesicles (EVs) are nanosized membrane-bound particles released from all living cells examined thus far. EVs can transfer information in the form of proteins, nucleic acids, and lipids from donor cells to recipient cells. Here we summarize recent advances in understanding the role(s) EVs play in hematological malignancies (HM) and outline potential prognostic and diagnostic strategies using EVs. EVs have been shown to promote proliferation and angiogenesis, and alter the bone marrow microenvironment to favour the growth and survival of diverse HM. They also promote evasion of anti-cancer immune responses and increase multi-drug resistance. Using knowledge of EV biology, including HM-specific packaging of cargo, EV based diagnostics and therapeutic approaches show substantial clinical promise. However, while EVs may represent a new paradigm to solve many of the challenges in treating and/or diagnosing HM, much work is needed before they can be used clinically to improve patient outcomes.
