Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia

Péterffy, Borbála and Nádasi, Tamás and Krizsán, Szilvia and Horváth, Anna and Márk, Ágnes and Barna, Gábor and Tímár, Botond and Almási, Laura and Müller, Judit and Csanádi, Krisztina and Rakonczai, Anna and Nagy, Zsolt and Kállay, Krisztián and Kertész, Gabriella and Kriván, Gergely and Csóka, Mónika and Sebestyén, Anna and Semsei, Ágnes and Kovács, Gábor and Erdélyi, Dániel and Bödör, Csaba and Egyed, Bálint and Alpár, Donát (2024) Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia. SCIENTIFIC REPORTS, 14. No 28556. ISSN 2045-2322

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Abstract

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status. Normalized copy number of miR-181a was longitudinally profiled using droplet digital PCR, and the results were compared with the degree of leukemic involvement of the CNS. After combining cytospin- and flow cytometry (FCM) data with miR-181a expression, we could stratify previously ambiguous cases and reclassify patients into a CNSpositive/ miR-significant group (mean ± SE for miR-181a copies: 3300.70 ± 809.69) bearing remarkable infiltration as well as into CNS-minimal/miR-significant and CNS-minimal/miR-minimal groups differentiating putative, clinically significant occult CNSL cases (2503.50 ± 275.89 and 744.02 ± 86.81 copies, respectively, p = 1.13 × 10–6). In summary, miR-181a expression is a promising biomarker for CNSL detection, facilitating the robust identification of patients who could benefit from intensified CNS-directed therapy.

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