Disease relevance of PRAME

• Conversely, knockdown of PRAME expression by RNA interference in RA-resistant human melanoma restores RAR signaling and reinstates sensitivity to the antiproliferative effects of RA in vitro and in vivo [1].
• CONCLUSIONS: PRAME expression in neuroblastoma is extraordinarily common and was universally seen in patients with advanced-stage disease in our study [2].
• Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia (CML) in blastic crisis and Philadelphia (Ph)+-acute lymphoblastic leukemia (ALL), in which BCR/ABL played an important role as a pathogenic gene [3].
• Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia [4].
• We have screened 98 Japanese patients with leukaemia and lymphoma for expression of the PRAME gene using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) [4].

High impact information on PRAME

• The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling [1].
• PRAME is present at RAR target promoters and inhibits RA-induced differentiation, growth arrest, and apoptosis [1].
• CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA(100-108); SLYSFPEPEA, PRA(142-151); ALYVDSLFFL, PRA(300-309); and SLLQHLIGL, PRA(425-433)) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A(*)0201 [5].
• We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A(*)0201-presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved "reverse immunology" strategy [5].
• Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis [5].

Biological context of PRAME

• EXPERIMENTAL DESIGN: Qualitative analysis of PRAME expression was assessed by reverse transcription (RT)-PCR screening of 94 patients with primary neuroblastoma [2].
• PRAME gene expression in childhood acute lymphoblastic leukemia [6].
• Cells stably transfected with PRAME also exhibit a decreased proliferation rate due, at least partially, to an elevated basal rate of cell death [7].
• On these clinical observations, we assumed that PRAME could be involved in the regulation of cell death or cell cycle [7].
• Our results indicate that patients showing PRAME upregulation may have an increased risk of MDR induction [8].

Anatomical context of PRAME

• The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells [9].
• We show that malignant plasma cells from the majority of MM patients (n = 21) expressed MAGE-1, MAGE-3 and PRAME [9].
• PRAME (10 of 14 cell lines), RAGE-1 (7 of 14 cell lines), and gp75 (4 of 14 cell lines) antigens were expressed in a high percentage of RCC cell lines, although the level of TAA expression varied among the different RCC cell lines [10].
• Thus PRAME was considered to be a good candidate for a marker of Ph+-leukemic blast cells as well as a new target antigen of leukemic blast cells that cytotoxic T cells can recognize [3].
• We tested by RT-PCR the expression of PRAME on more than 250 bone marrow or blood samples from patients with a haematological malignancy [11].

Regulatory relationships of PRAME

• PRAME (Preferentially expressed antigen of melanoma) has been previously identified as a melanoma antigen recognized by cytotoxic T cells (CTLs) and found to be expressed in a variety of cancer cells including leukaemic cells [4].

Other interactions of PRAME

• Furthermore, association with tumor stage, age of patients at diagnosis, and MYCN amplification was determined as well as the prognostic impact of PRAME expression [2].
• The cancer/testis-specific antigens such as MAGE and PRAME should potentially be highly immunogenic antigens [12].
• Cloning and sequencing of a gene which was upregulated in ID-1 cells revealed that the gene was identical to a melanoma antigen, PRAME [3].
• Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene [3].
• In this study, quantitative reverse transcriptase polymerase chain reaction was used to measure PRAME gene expression in 50 children with newly diagnosed acute lymphoblastic leukemia (ALL) [6].

Analytical, diagnostic and therapeutic context of PRAME

• For more precise quantification of PRAME expression, real-time RT-PCR was performed in 88 patients of the above cohort and 7 additional patients, thus leaving a total of 101 patients that were analyzed with either method [2].
• Therefore, quantitative monitoring of the PRAME gene using real-time PCR method may be useful for detecting minimal residual disease and to predict subsequent relapse, especially in patients without known genetic markers [4].
• Significant reductions in the PRAME expression were observed in all patients after chemotherapy [4].
• This might constitute a problem in using PRAME for tumor immunotherapy [13].
• In accordance with our findings in acute myeloblastic leukemia (AML) patients, the rate of disease-free survival was higher and white blood cell counts at diagnosis were lower in patients with an overexpression of PRAME [6].

References