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Epigenetic regulation of PRAME gene in chronic myeloid leukemia.

Research paper by Jose J Roman-Gomez, Antonio A Jimenez-Velasco, Xabier X Agirre, Juan A JA Castillejo, German G Navarro, Edurne San ES Jose-Eneriz, Leire L Garate, Lucia L Cordeu, Francisco F Cervantes, Felipe F Prosper, Anabel A Heiniger, Antonio A Torres

Indexed on: 27 Mar '07Published on: 27 Mar '07Published in: Leukemia Research



Abstract

Tumor associated antigens (TAA) provide attractive targets for cancer-specific immunotherapy. PRAME is a TAA gene up-regulated in advanced phases of chronic myeloid leukemia (CML). To date, molecular mechanisms for the expression of PRAME have never been studied. We found that some Ph'-positive cell lines did not express PRAME. The expression of PRAME was restored in these cell lines by treatment with 5'-aza-2'-deoxycytidine, suggesting that the expression of PRAME is mainly suppressed by hypermethylation. Bisulfite sequencing analysis of the CpG sites of the PRAME exon 2 in these cancer cell lines revealed a close relationship between the methylation status of the PRAME gene and its expression. A methylation-specific PCR analysis demonstrated that hypomethylation of PRAME was significantly more frequent in CML blast crisis (70%) than in chronic phase (36%) (P=0.01) and was correlated with high expression levels of PRAME transcripts (P<0.0001). These results suggest that hypomethylation of PRAME up-regulates its expression in CML and might play a significant role in the progression of the disease.

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