Alternative titles; symbols
HGNC Approved Gene Symbol: PRAME
Cytogenetic location: 22q11.22 Genomic coordinates (GRCh38) : 22:22,547,701-22,559,265 (from NCBI)
Human tumor antigens recognized by autologous cytolytic T lymphocytes (CTLs) include 3 classes of proteins: those expressed in tumors but not in normal tissues other than placenta or testis (e.g., MAGE1; 300016); differentiation antigens expressed in melanocytes or melanomas (e.g., melan A; 605513); and antigens resulting from point mutations in ubiquitously expressed genes (e.g., MUM1; 601900). The melanoma cell lines MEL.A and MEL.B were derived from metastases removed from a patient (LB33) in 1988 and 1993, respectively. MEL.A cells express several antigens recognized by CTLs on HLA class I molecules, while MEL.B cells have lost expression of class I molecules except HLA-A24 (Ikeda et al., 1997).
By stimulating peripheral blood lymphocytes collected from patient LB33 in 1994 with irradiated MEL.B cells, Ikeda et al. (1997) isolated CTLs specific for an antigen they termed LB33-E, which was presented by HLA-A24. They identified cDNAs encoding antigen LB33-E, which correspond to a gene they designated PRAME (preferentially expressed antigen in melanoma). The deduced 509-amino acid PRAME protein contains no signal sequence. Northern blot analysis detected 2.2- and 3.0-kb PRAME transcripts in tumor cell lines but not in normal tissue except testis. RT-PCR analysis detected very low expression of PRAME in ovary and adrenals. Functional analysis showed that PRAME-specific CTLs can lyse MEL.B but not MEL.A cells due to inhibition mediated by the interaction of a p58.2 molecule (KIR2DL2; 604937) on the CTLs with HLA-Cw7 on the melanoma target cell.
Neisseria gonorrhoeae opacity-associated (Opa) proteins are a family of outer membrane proteins involved in gonococcal adhesion to and invasion of human cells. Opa expression appears to be necessary for gonococcal disease. Using the yeast 2-hybrid system to screen a HeLa cell cDNA library with an N. gonorrhoeae Opa protein as bait, Williams et al. (1998) identified partial cDNAs encoding Opa-interacting protein-1 (OIP1, or TRIP6; 602933), OIP2 (606019), OIP3 (PK3; 179050), OIP4, and OIP5 (606020). Sequence analysis predicted that OIP4 encodes a 58-amino acid peptide that is 100% identical to the C terminus of PRAME. OIP4 contains a cluster of basic residues and a cysteine motif.
Using RT-PCR analysis, van Baren et al. (1998) determined that 25% of acute leukemia, 35% of acute myeloid leukemia (AML), and 15% of acute lymphoid leukemia samples expressed PRAME. The association was highest in AML tumors carrying t(8;21) or t(15;17) (96% and 45%, respectively), chromosomal abnormalities that have a relatively favorable prognosis.
Epping et al. (2005) identified PRAME as a dominant repressor of retinoic acid receptor (see, e.g., RARA; 180240) signaling. PRAME bound to RAR in the presence of retinoic acid, preventing receptor activation, and PRAME expression conferred resistance to retinoic acid-induced proliferation arrest, differentiation, and apoptosis. Knockdown of PRAME in melanoma cells using siRNA restored RAR signaling and reinstated sensitivity to the antiproliferative effects of retinoic acid in vitro and in vivo. Epping et al. (2005) noted that PRAME is overexpressed in a variety of cancers, and likely confers growth or survival advantages in these cells by antagonizing RAR signaling.
Stumpf (2024) mapped the PRAME gene to chromosome 22q11.22 based on an alignment of the PRAME sequence (GenBank BC014074) with the genomic sequence (GRCh38).
Epping, M. T., Wang, L., Edel, M. J., Carlee, L., Hernandez, M., Bernards, R. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122: 835-847, 2005. [PubMed: 16179254] [Full Text: https://doi.org/10.1016/j.cell.2005.07.003]
Ikeda, H., Lethe, B., Lehmann, F., van Baren, N., Baurain, J.-F., de Smet, C., Chambost, H., Vitale, M., Moretta, A., Boon, T., Coulie, P. G. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6: 199-208, 1997. [PubMed: 9047241] [Full Text: https://doi.org/10.1016/s1074-7613(00)80426-4]
Stumpf, A. M. Personal Communication. Baltimore, Md. 01/03/2024.
van Baren, N., Chambost, H., Ferrant, A., Michaux, L., Ikeda, H., Millard, I., Olive, D., Boon, T., Coulie, P. G. PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Brit. J. Haemat. 102: 1376-1379, 1998. [PubMed: 9753074] [Full Text: https://doi.org/10.1046/j.1365-2141.1998.00982.x]
Williams, J. M., Chen, G.-C., Zhu, L., Rest, R. F. Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth. Molec. Microbiol. 27: 171-186, 1998. [PubMed: 9466265] [Full Text: https://doi.org/10.1046/j.1365-2958.1998.00670.x]