MicroRNA-29c and microRNA-223
downregulation has in vivo significance in chronic lymphocytic leukemia
and improves disease risk stratification
Stamatopoulos
B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L,
Heimann P, Martiat P, Bron D and Lagneaux LStamatopoulos B, Meuleman N,
Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P,
Martiat P, Bron D and Lagneaux L
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 (HR
0/4<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.