A molecular score by quantitative PCR as a new prognostic tool at diagnosis for chronic lymphocytic leukemia patients

September 29, 2010

Blank A molecular score by quantitative PCR as a new prognostic tool at

diagnosis for chronic lymphocytic leukemia patients.

B Stamatopoulos, N Meuleman, C De Bruyn, K Pieters, G Anthoine, P Mineur, D

Bron, and L Lagneaux

PLoS One, January 1, 2010; 5(9): .

Laboratory of Experimental Hematology, Faculty of Medicine, Institut Jules

Bordet, Universit? Libre de Bruxelles (ULB), Brussels, Belgium.

BACKGROUND: Several markers have been proposed to predict the outcome of chronic

lymphocytic leukemia (CLL) patients. However, discordances exist between the

current prognostic factors, indicating that none of these factors are totally

perfect. METHODOLOGY/PRINCIPAL FINDINGS: Here, we compared the prognostic power

of new RNA-based markers in order to construct a quantitative PCR (qPCR) score

composed of the most powerful factors. ZAP70, LPL, CLLU1, microRNA-29c and

microRNA-223 were measured by real time PCR in a cohort of 170 patients with a

median follow-up of 64?months (range3-330). For each patient, cells were

obtained at diagnosis and RNA was extracted from purified CD19 cells. The best

markers were included in a qPCR score, which was thereafter compared to each

individual factor. Statistical analysis showed that all five RNA-based markers

can predict treatment-free survival (TFS), but only ZAP70, LPL and microRNA-29c

could significantly predict overall survival (OS). These three markers were thus

included in a simple qPCR score that was able to significantly predict TFS and

OS by dividing patients into three groups (0/3, 1-2/3 and 3/3). Median TFS were

>210, 61 and 24 months (P<0.0001) and median OS were >330, 242 and 137 months

(P<0.0001), respectively. Interestingly, TFS results were also confirmed in

Binet stage A patients (P<0.0001). When compared to other classical factors,

this score displays the highest univariate hazard ratio (TFS: HR?=?9.45 and

OS: HR?=?13.88) but also provides additional prognostic information.

CONCLUSIONS: In our hands, this score is the most powerful tool for CLL risk

stratification at the time of diagnosis.

PMID: 20862275

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