Epigenetic regulation of PRAME gene in chronic myeloid leukemia.
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.
Roman-Gomez
Jose
J
Hematology Department, Reina Sofia Hospital, Avda, Menendez Pidal s/n, 14004, Cordoba, Spain. peperosa@teleline.es
Jimenez-Velasco
Antonio
A
Agirre
Xabier
X
Castillejo
Juan A
JA
Navarro
German
G
Jose-Eneriz
Edurne San
ES
Garate
Leire
L
Cordeu
Lucia
L
Cervantes
Francisco
F
Prosper
Felipe
F
Heiniger
Anabel
A
Torres
Antonio
A
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
D000951:Antigens, Neoplasm; D017931:DNA Primers; C404944:PRAME protein, human; D012333:RNA, Messenger