{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:15:28Z","timestamp":1787724928247,"version":"build-2784847793"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cole Foundation","award":["BIO20\/CI\/016\/BIOEF"],"award-info":[{"award-number":["BIO20\/CI\/016\/BIOEF"]}]},{"name":"NSERC","award":["BIO20\/CI\/016\/BIOEF"],"award-info":[{"award-number":["BIO20\/CI\/016\/BIOEF"]}]},{"name":"Fundaci\u00f3n Vasca de Innovaci\u00f3n e Investigaci\u00f3n Sanitarias","award":["BIO20\/CI\/016\/BIOEF"],"award-info":[{"award-number":["BIO20\/CI\/016\/BIOEF"]}]},{"name":"NRC under the Pandemic Response Challenge Program","award":["BIO20\/CI\/016\/BIOEF"],"award-info":[{"award-number":["BIO20\/CI\/016\/BIOEF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Analysis of tumoral RNA from bone marrow (BM) biopsy is essential for diagnosing childhood B-cell acute lymphoblastic leukemia (B-ALL), risk stratification, and monitoring, by detecting fusions and gene expression patterns. However, frequent BM biopsies are invasive and traumatic for patients. Small extracellular vesicles (sEVs) circulating in blood contain a variety of biomolecules, including RNA, that may contribute to cancer progression, offering a promising source of non-invasive biomarkers from liquid biopsies. While most EV studies have focused on small RNAs like microRNAs (miRNAs), the role of longer RNA species, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), remains underexplored despite their demonstrated potential for risk-based patient stratification when starting from BM biopsies. We used immuno-purification to isolate sEVs from peripheral blood at diagnosis in B-ALL patients and cell model-based conditioned culture medium (CCM) with ETV6::RUNX1 and TCF3::PBX1 fusions. Using whole-transcriptome sequencing targeting transcripts over 200 nt and a novel data analysis pipeline, we identified 102 RNA transcripts (67 mRNAs, 16 lncRNAs, 10 circRNAs, 4 pseudogenes, and 5 others) in patient-derived sEVs. These transcripts could serve as biomarkers for two distinct molecular subgroups of B-ALL, each with different risk profiles at diagnosis. This is the first study characterizing the long transcriptome in blood-derived sEVs for childhood B-ALL, highlighting the potential use of circulating RNAs for improved risk-based stratification.<\/jats:p>","DOI":"10.3390\/ijms26093956","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long Circulating RNAs Packaged in Extracellular Vesicles: Prospects for Improved Risk Assessment in Childhood B-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1376-9367","authenticated-orcid":false,"given":"Lucas","family":"Poncelet","sequence":"first","affiliation":[{"name":"Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"},{"name":"Medical Devices Research Centre, National Research Council Canada, Boucherville, QC J4B 6Y4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Richer","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Gutierrez-Camino","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"},{"name":"Pediatric Oncology Group, BioBizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor","family":"Veres","sequence":"additional","affiliation":[{"name":"Medical Devices Research Centre, National Research Council Canada, Boucherville, QC J4B 6Y4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-6676","authenticated-orcid":false,"given":"Daniel","family":"Sinnett","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"},{"name":"Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2162-3619-3-16","article-title":"Childhood B-acute lymphoblastic leukemia: A genetic update","volume":"3","author":"Woo","year":"2014","journal-title":"Exp. 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