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PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute
N van Baren1, H Chambost, A Ferrant
1Cellular Genetics Unit, Université Catholique de Louvain, Brussels, Belgium.
Abstract:
Gene PRAME was found to encode an antigen recognized on a human melanoma cell line by an autologous cytolytic T-lymphocyte clone. This gene is expressed at a high level in a very large fraction of tumours, such as melanomas, non-small-cell lung carcinomas, sarcomas, head and neck tumours and renal carcinomas. It is therefore a candidate for tumour immunotherapy even though some low expression is found in certain normal tissues. We tested by RT-PCR the expression of PRAME on more than 250 bone marrow or blood samples from patients with a haematological malignancy. Approximately 25% of the acute leukaemia samples were positive. Remarkably, all acute myeloblastic leukaemias that carried the chromosomal translocation t(8;21), which fuses the genes AML1 and ETO, expressed PRAME at a high level.
Insights
The PRAME gene encodes an antigen found on melanoma cells. High PRAME gene expression in various tumors, including acute myeloid leukemia with t(8;21) translocation, suggests its potential for cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The PRAME gene encodes an antigen recognized by autologous cytolytic T-lymphocytes on melanoma cells.
- PRAME exhibits high-level expression in a significant proportion of diverse tumors, including melanomas, non-small-cell lung carcinomas, sarcomas, head and neck tumors, and renal carcinomas.
- Despite some expression in normal tissues, PRAME is a candidate for tumor immunotherapy.
Purpose of the Study:
- To investigate the expression of the PRAME gene in hematological malignancies.
- To assess the correlation between PRAME expression and specific genetic alterations in leukemia.
Main Methods:
- Reverse Transcription Polymerase Chain Reaction (RT-PCR) was employed to analyze PRAME gene expression.
- Over 250 bone marrow or blood samples from patients with hematological malignancies were tested.
Main Results:
- PRAME expression was detected in approximately 25% of acute leukemia samples.
- A notable finding was the high-level expression of PRAME in all tested acute myeloblastic leukemia samples harboring the t(8;21) chromosomal translocation.
- The t(8;21) translocation involves the fusion of the AML1 and ETO genes.
Conclusions:
- The PRAME gene is frequently expressed in hematological malignancies, particularly in specific subtypes of acute myeloid leukemia.
- High PRAME expression in t(8;21) positive acute myeloid leukemia suggests a potential role for PRAME-targeted therapies in this patient group.
- Further research into PRAME as a therapeutic target in cancer, especially leukemia, is warranted.