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The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia

¹ Hospital Universitario, Salamanca, Spain
² Centro de Investigación del Cáncer-IBMCC (USAL-CSIC) of Salamanca, Spain
³ Complejo Hospitalario de Leon, Spain
⁴ Hospital Central de Asturias, Oviedo, Spain
⁵ Hospital General de Segovia, Spain
⁶ Hospital Rìo Hortega, Valladolid, Spain and
⁷ Hospital Miguel Servet, Zaragoza, Spain

Correspondence: Ramon Garcia-Sanz, MD, PhD, Department of Hematology, University Hospital of Salamanca, Paseo de san Vicente, 58-182, Salamanca 37007 Spain. E-mail:rgarcias{at}usal.es

ABSTRACT

Background: The gene for preferentially expressed antigen of melanoma (PRAME) has been shown to be over-expressed in acute promyelocytic leukemia, but its actual incidence and clinical impact are still unknown

Design and Methods: We studied PRAME expression at diagnosis using real-time quantitative polymerase chain reaction in 125 patients with acute promyelocytic leukemia enrolled in the Spanish PETHEMA-96 (n=45) and PETHEMA-99 (n=80) clinical trials. In addition, PRAME expression was evaluated as a marker of disease activity in 225 follow-up samples from 67 patients with acute promyelocytic leukemia.

Results: At diagnosis, PRAME expression in patients with acute promyelocytic leukemia was significantly higher (p<0.001) than in patients with both non-M3 acute myeloid leukemia (n=213) and healthy controls (n=10). Furthermore, patients with acute promyelocytic leukemia with high PRAME expression had a favorable outcome. Thus, the 5-year relapse-free survival was better in patients with >100-fold PRAME expression (86% vs. 74%; p=0.03), and this cut-off established two sub-groups with different relapse-free survival rates among patients with a white cell count <10⁹/L (5-year RFS 94% vs. 80%, p=0.01). This effect was similar in patients with white cell count >10⁹/L, although differences were not statistically significant. In multivariate analysis, white cell count >10⁹/L (p<0.001), bone marrow blasts >90% (p=0.001), and PRAME expression <100-fold (p=0.009) were associated with short relapse-free survival. Samples at remission showed PRAME levels similar to those in normal controls while samples at relapse over-expressed PRAME again. Furthermore, 12/13 samples collected within the 6-month period preceding relapse showed a >10-fold increase in PRAME expression levels.

Conclusions: Low PRAME expression defines a subgroup of patients with acute promyelocytic leukemia with a short relapse-free survival. This marker could be useful as a secondary marker for monitoring patients with acute promyelocytic leukemia.

Key words: acute promyelocytic leukemia, PRAME, real time quantitative PCR.