Epigenetic regulation of PRAME gene in chronic myeloid leukemia
Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, Jose-Eneriz ES, Garate L, Cordeu L, Cervantes F, Prosper F, Heiniger A, Torres A.
Hematology Department, Reina Sofia Hospital, Avda, Menendez Pidal s/n, 14004, Cordoba, Spain.
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.
CITATION Leuk Res. 2007 Nov;31(11):1521-8