microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification.
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.
Stamatopoulos
Basile
B
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. bstamato@ulb.ac.be
Meuleman
Nathalie
N
Haibe-Kains
Benjamin
B
Saussoy
Pascale
P
Van Den Neste
Eric
E
Michaux
Lucienne
L
Heimann
Pierre
P
Martiat
Philippe
P
Bron
Dominique
D
Lagneaux
Laurence
L
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
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