title: Epigenetic regulation of PRAME gene in chronic myeloid leukemia.
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.
authors: Hematology Department, Reina Sofia Hospital, Avda, Menendez Pidal s/n, 14004, Cordoba, Spain. peperosa@teleline.es
authors: Jose
authors: J
authors: Roman-Gomez
authors: Antonio
authors: A
authors: Jimenez-Velasco
authors: Xabier
authors: X
authors: Agirre
authors: Juan A
authors: JA
authors: Castillejo
authors: German
authors: G
authors: Navarro
authors: Edurne San
authors: ES
authors: Jose-Eneriz
authors: Leire
authors: L
authors: Garate
authors: Lucia
authors: L
authors: Cordeu
authors: Francisco
authors: F
authors: Cervantes
authors: Felipe
authors: F
authors: Prosper
authors: Anabel
authors: A
authors: Heiniger
authors: Antonio
authors: A
authors: Torres
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D044127:Epigenesis, Genetic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D017931:DNA Primers; C404944:PRAME protein, human; D012333:RNA, Messenger