High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation

The PReferentially expressed Antigen of the Melanoma Gene (PRAME) has been shown to be overexpressed in multiple solid cancers and in human germ-line tissues but only weakly expressed, if at all, in other healthy tissues leading to its classification as a cancer-testis (CT) antigen. High expression of PRAME has been associated with poor survival and shortened disease-free survival in a number of solid cancers. However, evidence of an association between PRAME expression and survival in haematological malignancies has not been so clear. In acute promyelocytic leukaemia, typified by the t(15;17) translocation, low PRAME expression has indicated shortened overall survival (OS) (Santamaria et al, 2008), while high PRAME expression has also been associated with t(8;21), a favourable cytogenetic aberration, in acute myeloid leukaemia (AML) patients (van Baren et al, 1998). In addition, PRAME expression was found to be associated with progression-free survival or OS in acute leukaemia by some groups (Greiner et al, 2006; Tajeddine et al, 2008) but not others (Paydas et al, 2005; Guinn et al, 2009). Evidence for the direct involvement of PRAME in carcinogenesis and disease progression was demonstrated in acute leukaemia cells when PRAME inhibition was shown to lead to apoptosis (Tanaka et al, 2011). However, other groups have reported that high expression of PRAME is a marker of a favourable outcome and good OS may be partly due to its association with a decreased expression of several other genes (HSPB1, S100A4, CDKN1A, IL8 and IGFBP2) in childhood AML patients (Tajeddine et al, 2008).