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Title

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

AuthorsSantamaría, Carlos; Chillón, M. del Carmen; García-Sanz, Ramón; Balanzategui, Ana; Sarasquete, María Eugenia; Alcoceba, Miguel; San Miguel, Jesús F. ; González, Marcos
Issue Date2008
PublisherFerrata Storti Foundation
CitationHaematologica 93(12): 1797-1805 (2008)
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 non-M3 acute myeloid leukemia (n=213) and in 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 relapse-free survival 94% vs. 80%, p=0.01). This effect was similar in patients with a 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. ©2008 Ferrata Storti Foundation.
URIhttp://hdl.handle.net/10261/63645
DOI10.3324/haematol.13214
Identifiersdoi: 10.3324/haematol.13214
issn: 0390-6078
Appears in Collections:(IBMCC) Artículos
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