title: microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification.
abstract: Aberrant expression of microRNAs has been recently associated with chronic lymphocytic leukemia (CLL) outcome. Although disease evolution can be predicted by several prognostic factors, a better outcome individualization in a given patient is still of utmost interest. Here, we showed that miR-29c and miR-223 expression levels decreased significantly with progression from Binet stage A to C were significantly lower in poor prognostic subgroups (defined by several prognostic factors) and could significantly predict treatment-free survival (TFS) and overall survival (OS). Furthermore, we developed a quantitative real-time polymerase chain reaction (qPCR) score combining miR-29c, miR-223, ZAP70, and LPL (from 0 to 4 poor prognostic markers) to stratify treatment and death risk in a cohort of 110 patients with a median follow-up of 72 months (range, 2-312). Patients with a score of 0/4, 1/4, 2/4, 3/4, and 4/4 had a median TFS of greater than 312, of 129, 80, 36, and 19 months, respectively (hazard ratio, HR(0/4 < 1/4 < 2/4 < 3/4 < 4/4) = 17.00, P < .001). Patients with a score of 0-1/4, 2-3/4, and 4/4 had a median OS of greater than 312, of 183 and 106 months, respectively (HR(0/4 < 1/4 < 2/4 < 3/4 < 4/4) = 13.69, P = .001). This score will help to identify, among the good and poor prognosis subgroups, patients who will need early therapy and thus will require a closer follow-up.
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. bstamato@ulb.ac.be
authors.forename: Basile
authors.initials: B
authors.lastname: Stamatopoulos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meuleman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.forename: Pascale
authors.initials: P
authors.lastname: Saussoy
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.forename: Pierre
authors.initials: P
authors.lastname: Heimann
authors.forename: Philippe
authors.initials: P
authors.lastname: Martiat
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis*; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D018570:Risk Assessment; D012720:Severity of Illness Index; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D008071:Lipoprotein Lipase; D035683:MicroRNAs; D012333:RNA, Messenger; D051746:ZAP-70 Protein-Tyrosine Kinase; C525067:MIR223, human; C532045:MIRN29a microRNA, human; C497261:ZAP70 protein, human