2009
DOI: 10.4149/neo_2009_06_514
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Activation of HLA-G expression by 5-aza-2´- deoxycytidine in malignant hematopoetic cells isolated from leukemia patients

Abstract: Human leukocyte antigen - G (HLA-G) is a non-classical HLA class I antigen with restricted distribution in normal tissues. Ectopic HLA-G expression observed at some pathological circumstances as malignant transformation might be triggered by epigenetic modifications such as DNA demethylation. Recently it was demonstrated that DNA methyltransferase inhibitor 5-aza-2 - deoxycytidine (AdC) induces/enhances HLA-G transcription in many leukemia cell lines of different origin. Here we investigated the effect of AdC … Show more

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Cited by 16 publications
(10 citation statements)
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“…CT using platinum compounds or paclitaxel showed significant reduction of HLA-G expression in tumor cells in patients with ovarian carcinoma [93]. In contrast, 5-aza-2 -deoxycytidine enhanced HLA-G in leukemia cells [97]. HLA-G was downregulated in basal cell carcinomas of the skin after RT [98].…”
Section: The Effect Of Ct/rt On Hla Molecule Expressionmentioning
confidence: 96%
“…CT using platinum compounds or paclitaxel showed significant reduction of HLA-G expression in tumor cells in patients with ovarian carcinoma [93]. In contrast, 5-aza-2 -deoxycytidine enhanced HLA-G in leukemia cells [97]. HLA-G was downregulated in basal cell carcinomas of the skin after RT [98].…”
Section: The Effect Of Ct/rt On Hla Molecule Expressionmentioning
confidence: 96%
“…These include epigenetic mechanisms, like CpG methylation and histone deacetylation [70, 106], or not yet identified factors, which negatively interfere with HLA-G expression [96]. So far, HLA-G methylation has been found not only in solid tumors, such as lung, colon, ovarian carcinoma and RCC, but also in hematopoietic malignancies [55, 70, 106108]. The level of HLA-G promoter methylation significantly differed in the tumor cells analyzed, as demonstrated by methylation-specific PCR, bisulfite sequencing as well as by combined bisulfite restriction analysis (COBRA).…”
Section: Molecular Mechanisms Involved In Impaired Hla-g Expressionmentioning
confidence: 99%
“…The level of HLA-G promoter methylation significantly differed in the tumor cells analyzed, as demonstrated by methylation-specific PCR, bisulfite sequencing as well as by combined bisulfite restriction analysis (COBRA). Treatment of HLA-G- tumor cells with 5-aza-2-desoxycytidine (DAC) reversed HLA-G repression by demethylation of the HLA-G promoter, which enhanced HLA-G transcription and protein expression in some leukemia and solid tumor cells [70, 108], but only rarely induced HLA-G [55, 109]. In normal non-malignant tissues and cell lines, HLA-G methylation has either not been demonstrated or only detected at a low frequency [55, 107].…”
Section: Molecular Mechanisms Involved In Impaired Hla-g Expressionmentioning
confidence: 99%
“…Treatment of a HLA-G-negative melanoma cell line with 5azaC restored HLA-G expression; similarly 5azaC activated HLA-G expression in human leukemia cell lines, even in malignant hematopoietic cells isolated from patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (B-CLL) (Polakova et al, 2009a;Polakova et al, 2009b). Further research found that HLA-G was silenced as a result of CpG hypermethylation within a 5′ regulatory region upstream of the start codon (Moreau et al, 2003;Yan et al, 2005).…”
Section: Hla-ligand Of Kirmentioning
confidence: 99%