association and clinical impact of PRAME mRNA expression in acute leukemias

ABSTRACT

PRAME [preferentially expressed antigen of melanoma] has been previously Identified as a melanoma antigen. It encodes an antigen recognized by autologous cytotoxic T lymphocytes. It shows no or very low expression in normal tissues, however a wide range of tumors including haemato-poietic neoplasias express this gene. The aim of this study is to detect PRAME gene expression in acute leukemias and to evaluate its clinical importance. Study and control groups consisted of thirty newly diagnosed cases of acute leukemia [15 AML and 15 ALL cases] and 10 age-matched healthy persons respectively. PRAME mRNA was detected by RT-PCR. Cases were monitored for 6 months and their treatment outcome was classified into responders and non responders. Initially PRAME positive responders were selected for re-evaluation of their PRAME expression by RT-PCR. Cases results in first admission showed that 50% of the studied leukemia cases expressed PRAME of which 66.7% AML cases and 33.3% ALL cases. Although the expression of PRAME was higher in AML than ALL, however the difference was not statistically significant. In particular PRAME was frequently expressed in AML M2 [40%], AML M3 [30%] and ALL L2 [80%], All normal controls did not express any PRAME mRNA transcript. The difference between patients and controls was statistically significant [p=0.00]. NO important correlation was found between PRAME expression, clinical and laboratory data such as age, sex, organomegally, lymphadenopathy, HB and blast%. As regards treatment outcome, PRAME positive cases were consistent more with poor outcome, although statistical companson of both groups did not reach statistical significance. BY reanalyzing PRAME expression in PRAME positive responders [5 cases], it was found that all cases still expressed PRAME mRNA transcript with the exception of one case. Hence a future possibillty to use PRAME as a marker to verify molecular remission and/or predict haematological remission/relapses should be particularly considered. Monitoring the levels of PRAME expression during the course of disease progression is absolutely indicated to postulate its potential as a marker for minimal residual disease. The impact of different treatment approaches on the levels of PRAME expression needs further investigations on a wider scale