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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5237-5245.
Prepublished online as a Blood First Edition Paper on January 14, 2009; DOI 10.1182/blood-2008-11-189407.
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Submitted November 14, 2008
Accepted January 3, 2009
MicroRNA-29c and microRNA-223 downregulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification
Basile Stamatopoulos*, Nathalie Meuleman, Benjamin Haibe-Kains, Pascale Saussoy, Eric Van den Neste, Lucienne Michaux, Pierre Heimann, Philippe Martiat, Dominique Bron, and Laurence Lagneaux
Laboratory of Experimental Hematology, Faculty of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles (ULB), Brussels, Belgium
Functional Genomics and Translational Research Unit, Faculty of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles (ULB), Brussels, Belgium
Cliniques Universitaires Saint Luc, Service de Biologie Hematologique, Brussels, Belgium
Center for Human Genetics, KU Leuven, Leuven, Belgium
Department of Medical Genetics, Erasme Hospital, Faculty of Medicine, Universite Libre de Bruxelles (ULB), Brussels, Belgium
* Corresponding author; email: bstamato{at}ulb.ac.be.
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 PCR 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 >312, 129, 80, 36 and 19 months, respectively (hazard ratio, HR0/4<1/4<2/4<3/4<4/4=17.00, P<0.0001). Patients with a score of 0-1/4, 2-3/4 and 4/4 had a median OS of >312, 183 and 106 months, respectively (HR0/4<1/4<2/4<3/4<4/4=13.69, P=0.0001). 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.
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