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Volume 16
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10.3390/biom16091293
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Article

Circulating Extracellular Vesicle Biomarkers in Chronic Lymphocytic Leukemia: A Preliminary Study on Their Diagnostic, Prognostic, and Predictive Relevance

by
Ilaria Laurenzana
1,
Antonella Caivano
2,*,
Alessio Di Ciancia
1,
Oreste Villani
3,
Maddalena Maietti
2,
Angelo De Stradis
4,
Giovanni D’Arena
5,
Filomena Nozza
1,†,
Luciana De Luca
2,* and
Daniela Lamorte
1
1
Laboratory of Preclinical and Translational Research, IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), via Padre Pio n. 1, 85028 Rionero in Vulture, Italy
2
Unit of Clinical Pathology, IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), via Padre Pio n. 1, 85028 Rionero in Vulture, Italy
3
Hematology and Stem Cell Transplantation Unit, IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), via Padre Pio n. 1, 85028 Rionero in Vulture, Italy
4
Institute for Sustainable Plant Protection, National Research Council (CNR), via G. Amendola n.122, 70126 Bari, Italy
5
Hematology, “S. Luca” Hospital, ASL Salerno, via Nizza n. 146, 84124 Salerno, Italy
*
Authors to whom correspondence should be addressed.
†
Present address: Pathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, viale O. Flacco n.63, 70124 Bari, Italy.
Biomolecules 2026, 16(9), 1293; https://doi.org/10.3390/biom16091293
Submission received: 28 July 2026 / Revised: 28 August 2026 / Accepted: 6 September 2026 / Published: 7 September 2026
(This article belongs to the Special Issue Extracellular Vesicles as Biomarkers of Diseases: 2nd Edition)
Versions Notes

Abstract

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by marked clinical heterogeneity, underscoring the need for reliable biomarkers to improve diagnosis and risk stratification. Extracellular vesicles (EVs) represent promising liquid biopsy candidates because they reflect the molecular profile of their cells of origin. In CLL, CD200 is a well-established marker of tumor cells; its expression on EVs and its role as a CLL biomarker were poorly characterized. This study investigated the diagnostic and prognostic value of serum EVs in CLL. Methods: Serum EVs were isolated from 83 patients with CLL and 20 healthy subjects (HS). EV morphology, size, and concentration were assessed by transmission electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to evaluate the expression of CD19, CD20, and CD200 on EVs, while digital PCR quantified EV-associated miR-93-5p, miR-125b-5p, miR-150-5p, and miR-484. Results: Compared with HS, CLL patients showed increased total EV counts and higher levels of CD19+, CD20+, CD200+, and CD19+/CD20+ EVs, together with enhanced CD20 and CD200 expression and reduced miR-93-5p, miR-125b-5p, and miR-484 levels. In contrast, EV-associated miR-150-5p levels were comparable between CLL patients and HS. EV features were correlated with clinical and biological characteristics, including disease stage, cytogenetic abnormalities, treatment, and time to treatment (TTT). Older age was associated with lower EV concentrations but higher CD20 and CD200 expression. Advanced-stage disease was characterized by smaller EVs with increased CD200 expression. Notably, elevated CD200+ EV levels and reduced CD19 expression were associated with shorter TTT and earlier treatment initiation. Conclusions: Multiparametric profiling identified distinct quantitative, phenotypic, and molecular features of CLL-derived EVs and revealed CD200 as a novel EV-associated biomarker. These findings support the clinical utility of serum EVs as a new valuable approach for CLL diagnosis, prognosis, and treatment prediction.
Keywords: extracellular vesicles; chronic lymphocytic leukemia; biomarkers; B cell antigens; CD200; microRNA; diagnosis; prognosis; prediction extracellular vesicles; chronic lymphocytic leukemia; biomarkers; B cell antigens; CD200; microRNA; diagnosis; prognosis; prediction

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MDPI and ACS Style

Laurenzana, I.; Caivano, A.; Di Ciancia, A.; Villani, O.; Maietti, M.; Stradis, A.D.; D’Arena, G.; Nozza, F.; De Luca, L.; Lamorte, D. Circulating Extracellular Vesicle Biomarkers in Chronic Lymphocytic Leukemia: A Preliminary Study on Their Diagnostic, Prognostic, and Predictive Relevance. Biomolecules 2026, 16, 1293. https://doi.org/10.3390/biom16091293

AMA Style

Laurenzana I, Caivano A, Di Ciancia A, Villani O, Maietti M, Stradis AD, D’Arena G, Nozza F, De Luca L, Lamorte D. Circulating Extracellular Vesicle Biomarkers in Chronic Lymphocytic Leukemia: A Preliminary Study on Their Diagnostic, Prognostic, and Predictive Relevance. Biomolecules. 2026; 16(9):1293. https://doi.org/10.3390/biom16091293

Chicago/Turabian Style

Laurenzana, Ilaria, Antonella Caivano, Alessio Di Ciancia, Oreste Villani, Maddalena Maietti, Angelo De Stradis, Giovanni D’Arena, Filomena Nozza, Luciana De Luca, and Daniela Lamorte. 2026. "Circulating Extracellular Vesicle Biomarkers in Chronic Lymphocytic Leukemia: A Preliminary Study on Their Diagnostic, Prognostic, and Predictive Relevance" Biomolecules 16, no. 9: 1293. https://doi.org/10.3390/biom16091293

APA Style

Laurenzana, I., Caivano, A., Di Ciancia, A., Villani, O., Maietti, M., Stradis, A. D., D’Arena, G., Nozza, F., De Luca, L., & Lamorte, D. (2026). Circulating Extracellular Vesicle Biomarkers in Chronic Lymphocytic Leukemia: A Preliminary Study on Their Diagnostic, Prognostic, and Predictive Relevance. Biomolecules, 16(9), 1293. https://doi.org/10.3390/biom16091293

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