<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">MIFTAKHOVA, REGINA</style></author><author><style face="normal" font="default" size="100%">SANDBERG, TOVE</style></author><author><style face="normal" font="default" size="100%">HEDBLOM, ANDREAS</style></author><author><style face="normal" font="default" size="100%">NEVZOROVA, TATYANA</style></author><author><style face="normal" font="default" size="100%">PERSSON, JENNY L.</style></author><author><style face="normal" font="default" size="100%">BREDBERG, ANDERS</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">DNA Methylation in ATRA-treated Leukemia Cell Lines Lacking a PML–RAR Chromosome Translocation</style></title><secondary-title><style face="normal" font="default" size="100%">Anticancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012-11-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">4715-4722</style></pages><volume><style face="normal" font="default" size="100%">32</style></volume><issue><style face="normal" font="default" size="100%">11</style></issue><abstract><style  face="normal" font="default" size="100%">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&lt;0.01) and U937 cells (p&lt;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.</style></abstract></record></records></xml>