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Blood, 15 July 2005, Vol. 106, No. 2, pp. 650-657.
Prepublished online as a Blood First Edition Paper on March 31, 2005; DOI 10.1182/blood-2004-08-3344.
Previous Article | Next Article 
Submitted August 30, 2004
Accepted February 25, 2005
The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia
Pablo Oppezzo, Yuri Vasconcelos, Catherine Settegrana, Dominique Jeannel, Francoise Vuillier, Magali Legarff-Tavernier, Eliza Yuriko Kimura, Stephane Bechet, Gerard Dumas, Martine Brissard, Helene Merle-Beral, Mihoko Yamamoto, Guillaume Dighiero, and Frederic Davi*
Unite d'Immuno-Hematologie et Immunopathologie, Institut Pasteur, Paris, France
Disciplina de Hematologia e Hemoterapia, Universade Federal de Sao Paulo, Sao Paulo, Brazil
Service d'Hematologie Biologique, Hopital Pitie-Salpetriere, Paris, France
Departement des Ecosystemes et Epidemiologie des Maladies Infectieuses, Institut Pasteur, Paris, France
Service Immunologie, Hopital Pitie-Salpetriere, Paris, France
Centre de Recherche Vaccinale et Biomedicale, Institut Pasteur, Paris, France
* Corresponding author; email: fred.davi{at}psl.ap-hop-paris.fr.
While ZAP-70 is over-expressed in CLL patients displaying unmutated IgVH genes and poor prognosis, a previous microarray study from our group identified overexpression of LPL and ADAM29 genes among unmutated and mutated CLLs respectively. To assess the prognostic value of these genes, we quantified their expression by RQ-PCR in a cohort of 127 CLL patients, and correlated this with clinical outcome, IgVH mutational status and ZAP-70 protein expression. IgVH mutational status, ZAP-70 and the LPL and ADAM29 mRNA ratios (L/A ratio) were predictive of event-free survival for the whole cohort and for stage A patients. In stage B and C patients, the L/A ratio was an independent prognostic factor while ZAP-70 did not predict survival. Simultaneous usage of the L/A ratio and ZAP-70 expression allowed an almost perfect (99%) assessment of the IgVH status in the 80% of patients with concordant results (L/A+, ZAP-70+ or L/A-, ZAP-70-). LPL and ADAM29 gene expression could also be determined by a simple competitive multiplex RT-PCR assay. Overall, quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognotic assessment than ZAP-70 in advanced stages of the disease.

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