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Mol. Life Sci."],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an extremely variable clinical course. We have recently shown that high catalase (<jats:italic>CAT<\/jats:italic>) expression identifies patients with an aggressive clinical course. Elucidating mechanisms regulating <jats:italic>CAT<\/jats:italic> expression in CLL is preeminent to understand disease mechanisms and develop strategies for improving its clinical management. In this study, we investigated the role of the <jats:italic>CAT<\/jats:italic> promoter rs1001179 single nucleotide polymorphism (SNP) and of the CpG Island II methylation encompassing this SNP in the regulation of <jats:italic>CAT<\/jats:italic> expression in CLL. Leukemic cells harboring the rs1001179 SNP T allele exhibited a significantly higher <jats:italic>CAT<\/jats:italic> expression compared with cells bearing the CC genotype. <jats:italic>CAT<\/jats:italic> promoter harboring the T -but not C- allele was accessible to ETS-1 and GR-\u03b2 transcription factors. Moreover, CLL cells exhibited lower methylation levels than normal B cells, in line with the higher CAT mRNA and protein expressed by CLL in comparison with normal B cells. Methylation levels at specific CpG sites negatively correlated with <jats:italic>CAT<\/jats:italic> levels in CLL cells. Inhibition of methyltransferase activity induced a significant increase in CAT levels, thus functionally validating the role of CpG methylation in regulating <jats:italic>CAT<\/jats:italic> expression in CLL. Finally, the CT\/TT genotypes were associated with lower methylation and higher <jats:italic>CAT<\/jats:italic> levels, suggesting that the rs1001179 T allele and CpG methylation may interact in regulating <jats:italic>CAT<\/jats:italic> expression in CLL. This study identifies genetic and epigenetic mechanisms underlying differential expression of <jats:italic>CAT<\/jats:italic>, which could be of crucial relevance for the development of therapies targeting redox regulatory pathways in CLL.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00018-022-04540-7","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T10:04:53Z","timestamp":1663322693000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The rs1001179 SNP and CpG methylation regulate catalase expression in chronic lymphocytic leukemia"],"prefix":"10.1007","volume":"79","author":[{"given":"Marilisa","family":"Galasso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Dalla Pozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Chignola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Gambino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cavallini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Maria","family":"Quaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Lovato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Dando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Malpeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Krampera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Donadelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G.","family":"Romanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-7859","authenticated-orcid":false,"given":"Maria T.","family":"Scupoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"4540_CR1","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1016\/S0140-6736(18)30422-7","volume":"391","author":"M Hallek","year":"2018","unstructured":"Hallek M, Shanafelt TD, Eichhorst B (2018) Chronic lymphocytic leukaemia. 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