5-Azacitidine induces demethylation of PTPL1 and inhibits growth in non-Hodgkin lymphoma

摘要

Non-Hodgkin lymphoma (NHL) consists of various lymphoid malignancies with a diverse clinical pathology and biological characteristics. Methylation of cytosine residues by DNA methyltransferases at CpG dinucleotides in the promoter region of the genes is a major epigenetic modification in mammalian genomes that can have profound effects on gene expression. The PTPL1 methylation pattern was screened by methylation-specific polymerase chain reaction (MSP) in 7 lymphoma-derived cell lines and in 47 samples of diffuse large B cell lymphoma (DLBCL). The PTPL1 gene was hypermethylated in the CA46, Raji, Jurkat and DB cell lines; however, it was unmethylated in the Hut78, Maver and Z138 cell lines. The expression of PTPL1 mRNA was re-inducible by 5-azacytidine (5-Aza), an agent of DNA demethylation. The methylations were detected in 59.6% of DLBCL versus 6.3% in reactive lymph node proliferation. Therefore, the present data showed that PTPL1 was epigenetically regulated in NHL suggesting an involvement of the PTPL1 tumor-suppressor genes in NHL, and highlights 5-Aza as a potential therapeutic candidate for NHL.