title: Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia.
abstract: MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL) physiopathology and prognosis. In addition, circulating microRNAs in body fluids have been proposed as new biomarkers. We investigated the expression of matched cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR) from purified CD19(+) cells or from CLL serums obtained at diagnosis in a cohort of 273/252 CLL patients with a median follow-up of 78 months (range 7-380) and correlated it to other biological or clinical parameters. We showed that miR-150 was significantly overexpressed in CLL cells/serums compared with healthy subjects (P < 0.0001). Among CLL patients, a low cellular miR-150 expression level was associated with tumor burden, disease aggressiveness and poor prognostic factors. In contrast, a high level of serum miR-150 was associated with tumor burden markers and some markers of poor prognosis. Similarly, cellular and serum miR-150 also predicted treatment-free survival (TFS) and overall survival (OS) in an opposite manner: patients with low cellular/serum miR-150 levels have median TFS of 40/111 months compared with high-level patients who have a median TFS of 122/60 months (P < 0.0001/P = 0.0066). Similar results were observed for OS. We also found that cellular and serum miR-150 levels vary in an opposite manner during disease progression and that cellular miR-150 could be regulated by its release into the extracellular space. Cellular and serum levels of miR-150 are associated with opposite clinical prognoses and could be used to molecularly monitor disease evolution as a new prognostic factor in CLL.
authors.affiliation: Laboratory of Clinical Cell Therapy, Faculty of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Basile
authors.initials: B
authors.lastname: Stamatopoulos
authors.affiliation: Laboratory of Clinical Cell Therapy, Faculty of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Michaël
authors.initials: M
authors.lastname: Van Damme
authors.affiliation: Laboratory of Clinical Cell Therapy, Faculty of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Emerence
authors.initials: E
authors.lastname: Crompot
authors.affiliation: Department of Genetics, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dessars
authors.affiliation: Department of Genetics, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Hakim El
authors.initials: HE
authors.lastname: Housni
authors.affiliation: Department of Hemato-Oncology, Grand Hôpital de Charleroi, Gilly, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mineur
authors.affiliation: Department of Hematology, Institut Jules Bordet, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meuleman
authors.affiliation: Department of Hematology, Institut Jules Bordet, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: Laboratory of Clinical Cell Therapy, Faculty of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008218:Lymphocytosis / Q000235:genetics; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C533097:MIR150, human