Extrachromosomal microDNA signature as a candidate biomarker in pediatric acute lymphoblastic leukemia

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Supplemental Table 1: Contingency table of shared microDNA producing genes	DOCX	18 KiB
Supplemental Figure 1: Graphical presentation of the micro-DNA signature gene	PNG	2.4 MiB
Supplemental Figure 2: Normalized mRNA expression of microDNA signature genes (log2FPKM+1) as obtained from RNA-seq data in controls and ALL cohorts stratified by relapse	PNG	4.0 MiB

DOI

Resolve DOI: https://doi.org/10.1158/2767-9764.CRC-25-0419

Author

Search for: Brukner, Ivan¹ORCID identifier: https://orcid.org/0000-0003-0225-9238; Search for: Gagné, Vincent²ORCID identifier: https://orcid.org/0009-0008-3809-3771; Search for: Richard-St-Hilaire, Alex²ORCID identifier: https://orcid.org/0009-0005-4718-0007; Search for: Tremblay-Dauphinais, Pascal²ORCID identifier: https://orcid.org/0009-0006-6052-3059; Search for: Fuchs, Claire²ORCID identifier: https://orcid.org/0000-0002-2202-907X; Search for: Bittencourt, Henrique²ORCID identifier: https://orcid.org/0000-0002-5507-8310; Search for: Veres, Teodor³ORCID identifier: https://orcid.org/0000-0002-9594-8042; Search for: Sinnett, Daniel²ORCID identifier: https://orcid.org/0000-0003-3625-6676; Search for: Krajinovic, Maja²ORCID identifier: https://orcid.org/0000-0003-4772-7031

Affiliation

McGill University
University of Montreal
National Research Council Canada. Medical Devices

Funder

Search for: Canadian Cancer Society; Search for: Leukemia and Lymphoma Society of Canada

Format

Text, Article

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite improved therapies, refractory and relapsed ALL remain the leading cause of cancer-related mortality in children. There is a need for accessible biomarkers for frequent, minimally invasive disease monitoring and prompt intervention. MicroDNA is a novel extrachromosomal DNA that preferentially originates from gene segments with high transcriptional activity and/or increased chromatin accessibility. We investigated whether microDNA-producing genes repertoire changes in a disease-dependent manner. We characterized microDNAs in 52 paired bone marrow (BM) and plasma samples from pediatric patients with ALL at diagnosis, relapse, and remission. No difference in the length or number of microDNA was noted across stages, but comparative analysis of microDNA profiles led to the identification of microDNA gene panels associated with active disease. The relative distribution of these genes was significantly different from that expected by chance (P < 0.0001). Analyses of BM samples identified a signature comprising 289 distinct microDNA-producing genes present in multiple patients at diagnosis and relapse but absent in remission. The best biomarker candidates were 11 microDNA-producing genes identified also in plasma samples at diagnosis and overrepresented in patients who relapsed (P = 0.006). MicroDNA from the same genes was confirmed in relapse plasma samples. All signature genes are known to be involved in cancer proliferation or drug response. MicroDNA seems to be a candidate for a novel class of biomarkers for ALL, with the potential to improve precision diagnostics, particularly through their identification in plasma samples. Further validation in an independent cohort of patients is warranted. Significance: Despite high cure rates, 10% to 15% of pediatric patients with ALL experience relapse. We identified a plasma-detectable microDNA signature from 11 genes that persists from diagnosis through relapse but disappears in remission. These findings demonstrate the potential of microDNA profiles as prognostic biomarkers in pediatric ALL, enabling noninvasive monitoring of disease status and risk stratification.

Publication date

2026-01-19

Publisher

American Association for Cancer Research

Licence

Creative Commons, Attribution 4.0 International (CC BY 4.0)
https://creativecommons.org/licenses/by/4.0/

Related data

Language

English

Peer reviewed

Yes

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Record identifier

62d73217-9c39-4dc6-be98-486617c22d32

Record created

2026-04-23

Record modified

2026-04-24

Page details

From:

National Research Council Canada

Date modified:: 2026-05-14