{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T13:08:26Z","timestamp":1782997706251,"version":"3.54.5"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,11,10]],"date-time":"2010-11-10T00:00:00Z","timestamp":1289347200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The sensitivity of chronic lymphocytic leukemia (CLL) cells to current treatments, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, relies on their ability to activate apoptotic death. CLL cells resistant to DNA damage-induced apoptosis display deregulation of a specific set of genes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Microarray hybridization (Human GeneChip, Affymetrix), immunofluorescent <jats:italic>in situ<\/jats:italic> labeling coupled with video-microscopy recording\/analyses, chromatin-immunoprecipitation (ChIP), polymerase chain reactions (PCR), real-time quantitative PCR (RT-QPCR) and bisulfite genome sequencing were the main methods applied. Statistical analyses were performed by applying GCRMA and SAM analysis (microarray data) and Student's t-test or Mann &amp; Whitney's U-test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Herein we show that, remarkably, in a resistant male CLL cells the vast majority of genes were down-regulated compared with sensitive cells, whereas this was not the case in cells derived from females. This gene down-regulation was found to be associated with an overall gain of heterochromatin as evidenced by immunofluorescent labeling of heterochromatin protein 1\u03b1 (HP-1), trimethylated histone 3 lysine 9 (3metH3K9), and 5-methylcytidine (5metC). Notably, 17 genes were found to be commonly deregulated in resistant male and female cell samples. Among these, <jats:italic>RELB<\/jats:italic> was identified as a discriminatory candidate gene repressed in the male and upregulated in the female resistant cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The molecular defects in the silencing of <jats:italic>RELB<\/jats:italic> involve an increase in H3K9- but not CpG-island methylation in the promoter regions. Increase in acetyl-H3 in resistant female but not male CLL samples as well as a decrease of total cellular level of RelB after an inhibition of histone deacetylase (HDAC) by trichostatin A (TSA), further emphasize the role of epigenetic modifications which could discriminate two CLL subsets. Together, these results highlighted the epigenetic <jats:italic>RELB<\/jats:italic> silencing as a new marker of the progressive disease in males.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1755-8794-3-53","type":"journal-article","created":{"date-parts":[[2010,11,10]],"date-time":"2010-11-10T19:14:29Z","timestamp":1289416469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Concomitant heterochromatinisation and down-regulation of gene expression unveils epigenetic silencing of RELBin an aggressive subset of chronic lymphocytic leukemia in males"],"prefix":"10.1186","volume":"3","author":[{"given":"Jean-Brice","family":"Marteau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Rigaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Brugat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Vallat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mogens","family":"Kruhoffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben F","family":"Orntoft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Nguyen-Khac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Chevillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Merle-Beral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozo","family":"Delic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,11,10]]},"reference":[{"key":"188_CR1","first-page":"334","volume":"79","author":"FR Mauro","year":"1994","unstructured":"Mauro FR, De RG, Burgio VL, Caruso R, Giannarelli D, Monarca B, Romani C, Baroni CD, Mandelli F: Prognostic value of bone marrow histology in chronic lymphocytic leukemia. 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