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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.

Authors: Santamaria, C  Chillon, MC  Garcia-Sanz, R  Balanzategui, A  Sarasquete, ME  Alcoceba, M  Ramos, F  Bernal, T  Queizan, JA  Penarrubia, MJ  Giraldo, P  San Miguel, JF  Gonzalez, M 
Citation: Santamaria C, etal., Haematologica. 2008 Dec;93(12):1797-805. doi: 10.3324/haematol.13214. Epub 2008 Sep 24.
Pubmed: (View Article at PubMed) PMID:18815192
DOI: Full-text: DOI:10.3324/haematol.13214

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 <10(9)/L (5-year relapse-free survival 94% vs. 80%, p=0.01). This effect was similar in patients with a white cell count >10(9)/L, although differences were not statistically significant. In multivariate analysis, white cell count >10(9)/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.

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CRRD Object Information
CRRD ID: 11535037
Created: 2016-09-19
Species: All species
Last Modified: 2016-09-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.