Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia

PRAME (Preferentially expressed antigen of melanoma) has been previously id entified as a melanoma antigen recognized by cytotoxic T cells (CTLs) and f ound to be expressed in a variety of cancer cells including leukaemic cells , We have screened 98 Japanese patients with leukaemia and lymphoma for exp ression of the FRAME gene using semiquantitative reverse transcription poly merase chain reaction (RT-PCR). Forty-one patients (42%) showed high levels of FRAME expression. Eight of these patients were then monitored using rea l-time PCR for a period of 10-37 months. Significant reductions in the FRAM E expression were observed in all patients after chemotherapy. An increased expression was detected in the two patients who relapsed, one of which was before cytological diagnosis, These changes were correlated with those of other known genetic markers, such as the bcr-abl gene. Therefore, quantitat ive monitoring of the PRAME gene using real-time PCR method may be useful f or detecting minimal residual disease and to predict subsequent relapse, es pecially in patients without known genetic markers. In addition, a PRAME-po sitive leukaemia cell line and fresh leukaemic cells were found to be susce ptible to lysis by FRAME-specific CTLs established from a patient with mela noma, suggesting that the PRAME peptide can also be a target leukaemia anti gen for T cells.