{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T18:19:54Z","timestamp":1715969994069},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:00:00Z","timestamp":1330387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD5<jats:sup>+<\/jats:sup> B\u2010cell malignancies with different biological\/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., <jats:italic>IGHV<\/jats:italic> mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylation and prognostic markers, such as the proliferation gene expression signature, has not been investigated in MCL. We applied high\u2010resolution methylation microarrays (27,578 CpG sites) to assess the global DNA methylation profiles in 20 MCL (10 each with high\/low proliferation signature) and 30 CLL (15 poor\u2010prognostic <jats:italic>IGHV<\/jats:italic> unmutated subset #1 and 15 good\u2010prognostic <jats:italic>IGHV<\/jats:italic> mutated subset #4) samples. Notably, MCL and each CLL subset displayed distinct genomic methylation profiles. After unsupervised hierarchical clustering, 17\/20 MCL cases formed a cluster separate from CLL, while CLL subsets #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes (<jats:italic>n<\/jats:italic> = 6) were identified between high vs. low proliferation MCL. In contrast, distinct methylation profiles were demonstrated for MCL and CLL. Importantly, certain functional classes of genes were preferentially methylated in either disease. For instance, developmental genes, in particular homeobox transcription factor genes (e.g., <jats:italic>HLXB9, HOXA13<\/jats:italic>), were more highly methylated in MCL, whereas apoptosis\u2010related genes were enriched among targets methylated in CLL (e.g., <jats:italic>CYFIP2, NR4A1<\/jats:italic>). Results were validated using pyrosequencing, RQ\u2010PCR and reexpression of specific genes. In summary, the methylation profile of MCL was homogeneous and no correlation with the proliferation signature was observed. Compared to CLL, however, marked differences were discovered such as the preferential methylation of homeobox genes in MCL. Am. J. Hematol., 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23115","type":"journal-article","created":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T12:55:34Z","timestamp":1326286534000},"page":"361-367","source":"Crossref","is-referenced-by-count":12,"title":["Mantle cell lymphoma displays a homogenous methylation profile: A comparative analysis with chronic lymphocytic leukemia"],"prefix":"10.1002","volume":"87","author":[{"given":"Anna Margr\u00e9t","family":"Halld\u00f3rsd\u00f3ttir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meena","family":"Kanduri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Millaray","family":"Marincevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Isaksson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"G\u00f6ransson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Axelsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasoon","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Jernberg\u2010Wiklund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kostas","family":"Stamatopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Sander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Ehrencrona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Rosenquist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,2,28]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"WHO Classification of Tumors of Hematopoietic and Lymphoid Tissue","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.8435"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199207000-00001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2230"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00028-X"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1848"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1840"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3485"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0132"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040544"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-012948"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07469.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006986"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2870"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-232868"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-257485"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019736"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404345"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20836"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.1.207"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23186"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20795"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1180"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07124.x"},{"key":"e_1_2_6_28_2","first-page":"8226","article-title":"The molecular signature of mantle cell lymphoma reveals multiple signals favoring cell survival","volume":"63","author":"Martinez N","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.4.14763"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2064"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701059104"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn115"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2826"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.38.072902.091907"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403057"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.07.014"},{"key":"e_1_2_6_37_2","first-page":"4398","article-title":"Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells","volume":"62","author":"Ek S","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.1.3665"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209601"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/38525"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4554"},{"key":"e_1_2_6_42_2","first-page":"7619","article-title":"Inactivation of a histone methyltransferase by mutations in human cancers","volume":"63","author":"Kim KC","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.870101"},{"key":"e_1_2_6_44_2","first-page":"8094","article-title":"Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone\/protein methyltransferase superfamily","volume":"61","author":"Du Y","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22325"},{"key":"e_1_2_6_46_2","first-page":"BR168","article-title":"SH3GL2 gene participates in MEK\u2010ERK signal pathway partly by regulating EGFR in the laryngeal carcinoma cell line Hep2","volume":"16","author":"Shang C","year":"2010","journal-title":"Med Sci Monit"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2464"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00840-08"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.471"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.298"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.23115","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.23115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T13:34:07Z","timestamp":1697463247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.23115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,28]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1002\/ajh.23115"],"URL":"https:\/\/doi.org\/10.1002\/ajh.23115","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,28]]}}}