DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation

DSpace Repository

DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation

Overview

Detailed record

dc.contributor.author Miftakhova, Regina
dc.contributor.author Sandberg, Tove
dc.contributor.author Hedblom, Andreas
dc.contributor.author Nevzorova, Tatyana
dc.contributor.author Persson, Jenny L.
dc.contributor.author Bredberg, Anders
dc.date.accessioned 2013-01-04T11:05:46Z
dc.date.available 2013-01-04T11:05:46Z
dc.date.issued 2012 en_US
dc.identifier.issn 1791-7530 en_US
dc.identifier.uri http://hdl.handle.net/2043/14790
dc.description.abstract Abstract A deficient retinoic acid signaling has been suggested to be an important cause of the clinical inefficacy of all-trans retinoic acid (ATRA) therapy in non-promyelocytic (non-PML) forms of acute myeloid leukemia (AML). The general aim of the present work was to explore novel ways to take advantage of the anti-leukemic potential of ATRA, and, specifically, to search for a synergism between ATRA and epigenetic drugs. Because previous reports have found no major influence of ATRA on DNA methylation, we investigated whether ATRA-mediated differentiation of the U937 and HL-60 AML cell lines, both lacking a PML-retinoic acid receptor (RAR) fusion product, is accompanied by early-appearing and weak changes in CpG methylation. We report that in HL-60 cells, by using a highly quantitative analysis of a set of genes found to be abnormally expressed in AML, polymerase chain reaction (PCR)-amplified p16 gene promoter molecules (each with 15 CpG sites), exhibited a CpG methylation level of 0-4% in untreated cells, which increased to 4-21% after treatment with ATRA for seven days. In contrast to HL-60 cells, U937 cells exhibited a very high CpG methylation level in p16, and ATRA did not influence the promoter methylation of this gene. In the total CCGG sites of the genome, analysed using a methylation-sensitive restriction enzyme, CpG methylation was significantly lower in ATRA-treated HL-60 (p<0.01) and U937 cells (p<0.05) than in controls. Taken together, our findings show that ATRA can influence DNA methylation, and suggest that future research should investigate whether epigenetic modulation may evoke a clinical effect of ATRA in leukemia. en_US
dc.format.extent 8
dc.language.iso eng en_US
dc.publisher International Institute of Anticancer Research en_US
dc.subject ATRA en_US
dc.subject DNA methylation en_US
dc.subject p16 en_US
dc.subject.classification Medicine en_US
dc.title DNA Methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome translocation en_US
dc.type Article, peer reviewed scientific en_US
dc.contributor.department Malmö University. Faculty of Health and Society en_US
dc.contributor.department Malmö University. Biomedical Sciences (BMV) en_US
dc.subject.srsc Research Subject Categories::MEDICINE en_US
dc.identifier.url http://ar.iiarjournals.org/content/32/11/4715.long en_US
dc.relation.ispartofpublication Anticancer Research;11
dc.relation.ispartofpublicationvolume 32 en_US
dc.format.ePage 4722
dc.format.sPage 4715
 Find Full text Files for download

There are no files associated with this item.

This item appears in the following Collection(s)

Overview

Search


Browse

My Account

Statistics