The Cancer Testis Antigen PRAME As a Biomarker for Solid Tumor Cancer Management

Abstract

Among the best-characterized tumor antigens are the cancer-testis antigens (CTAs), or germ cell antigens. These are a category of nonmutated genes that are restricted in expression to male germ cells and fetal tissues, but are detected in a variety of cancers and the cells derived from them. CTA gene families, including MAGE, BAGE, GAGE, LAGE/NY-ESO-1 and PRAME (preferentially expressed antigen of melanoma), encode antigenic peptides recognized by T lymphocytes. Numerous members of the CTA gene families are under intense study as targets for immunotherapy and as biomarkers for diagnosis and/or prognosis. Unlike other CTA genes, the PRAME gene (also known as MAPE or OIP4 ) has been shown to be expressed at low levels in ovarian, endometrial and adrenal tissues [1]. Originally characterized as a tumor antigen in a melanoma patient, PRAME is one of the best-characterized CTA family members because of its prevalence in both acute and chronic leukemias, and Hodgkin’s lymphoma [2]. Significant association of PRAME expression has been reported in acute myelogenous leukemia (AML), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloma and chronic myelogenous leukemia (CML). In CML, expression has been shown to correlate with disease progression [2,3]. PRAME has been reported to be an independent prognostic factor in AML, being associated with increased overall survival in patients with a favorable or poor prognoses based on karyotype [2,3]. The other area of promising clinical utility is disease stratification and the detection of residual disease. Although it varies according to disease type, the level of PRAME expression can indicate probable resistance to chemotherapy in lymphomas and AML [4]. PRAME expression has been observed to significantly decrease in