{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:35:20Z","timestamp":1791250520862,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2003,9,1]]},"DOI":"10.1038\/sj.leu.2403060","type":"journal-article","created":{"date-parts":[[2003,9,11]],"date-time":"2003-09-11T14:47:26Z","timestamp":1063291646000},"page":"1845-1850","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup"],"prefix":"10.1038","volume":"17","author":[{"given":"M I","family":"Gutierrez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A K","family":"Siraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bhargava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Ozbek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Banavali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"El Solh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2003,9,10]]},"reference":[{"key":"BF2403060_CR1","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1093\/nar\/10.8.2709","volume":"1","author":"M Ehrlich","year":"1982","unstructured":"Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 1982; 1: 2709\u20132721.","journal-title":"Nucleic Acids Res"},{"key":"BF2403060_CR2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/321209a0","volume":"321","author":"AP Bird","year":"1986","unstructured":"Bird AP . CpG-rich islands and the function of DNA methylation. Nature 1986; 321: 209\u2013213.","journal-title":"Nature"},{"key":"BF2403060_CR3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S0168-9525(98)01636-9","volume":"15","author":"PA Jones","year":"1999","unstructured":"Jones PA . The DNA methylation paradox. Trends Genet 1999; 15: 34\u201337.","journal-title":"Trends Genet"},{"key":"BF2403060_CR4","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/ng0495-407","volume":"9","author":"KD Tremblay","year":"1995","unstructured":"Tremblay KD, Saam JR, Ingram RS, Tilghman SM, Bartolomei MS . A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. Nat Genet 1995; 9: 407\u2013413.","journal-title":"Nat Genet"},{"key":"BF2403060_CR5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0168-9525(92)90219-T","volume":"8","author":"AD Riggs","year":"1992","unstructured":"Riggs AD, Pfeifer GP . X-chromosome inactivation and cell memory. Trends Genet 1992; 8: 169\u2013174.","journal-title":"Trends Genet"},{"key":"BF2403060_CR6","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0092-8674(83)90150-2","volume":"34","author":"M Busslinger","year":"1983","unstructured":"Busslinger M, Hurst J, Flavell RA . DNA methylation and the regulation of globin gene expression. Cell 1983; 34: 197\u2013206.","journal-title":"Cell"},{"key":"BF2403060_CR7","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1182\/blood.V93.12.4059","volume":"93","author":"R Singal","year":"1999","unstructured":"Singal R, Ginder GD . DNA methylation. Blood 1999; 93: 4059\u20134070.","journal-title":"Blood"},{"key":"BF2403060_CR8","doi-asserted-by":"publisher","first-page":"4842","DOI":"10.1073\/pnas.80.15.4842","volume":"80","author":"S Charache","year":"1983","unstructured":"Charache S, Dover G, Smith K, Talbot CC, Moyer M, Boyer S . Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex. Proc Natl Acad Sci USA 1983; 80: 4842\u20134846.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF2403060_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/path.1024","volume":"196","author":"M Esteller","year":"2002","unstructured":"Esteller M, Herman JG . Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumors. J Pathol 2002; 196: 1\u20137.","journal-title":"J Pathol"},{"key":"BF2403060_CR10","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/72785","volume":"25","author":"JF Costello","year":"2000","unstructured":"Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X et al. Aberrant CpG-island methylation has non-random and tumor-type-specific patterns. Nat Genet 2000; 25: 132\u2013138.","journal-title":"Nat Genet"},{"key":"BF2403060_CR11","doi-asserted-by":"publisher","first-page":"8681","DOI":"10.1073\/pnas.96.15.8681","volume":"96","author":"M Toyota","year":"1999","unstructured":"Toyota M, Ahuja N, Toyota MO, Herman JG, Baylin SB, Issa JP . CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999; 96: 8681\u20138686.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF2403060_CR12","first-page":"5438","volume":"59","author":"M Toyota","year":"1999","unstructured":"Toyota M, Ahuja N, Suzuki H, Itoh F, Toyota MO, Imai K et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 1999; 59: 5438\u20135442.","journal-title":"Cancer Res"},{"key":"BF2403060_CR13","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/S0002-9440(10)64059-X","volume":"158","author":"G Strathdee","year":"2001","unstructured":"Strathdee G, Appleton K, Illand M, Millan DWM, Sargent J, Paul J et al. Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes. Am J Pathol 2001; 158: 1121\u20131127.","journal-title":"Am J Pathol"},{"key":"BF2403060_CR14","doi-asserted-by":"publisher","first-page":"5427","DOI":"10.1038\/sj.onc.1205600","volume":"21","author":"M Esteller","year":"2002","unstructured":"Esteller M . CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 2002; 21: 5427\u20135440.","journal-title":"Oncogene"},{"key":"BF2403060_CR15","first-page":"880","volume":"48","author":"T Sakai","year":"1991","unstructured":"Sakai T, Toguchid J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP . Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet 1991; 48: 880\u2013888.","journal-title":"Am J Hum Genet"},{"key":"BF2403060_CR16","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1182\/blood.V93.12.4347","volume":"93","author":"RA Katzenellenbogen","year":"1999","unstructured":"Katzenellenbogen RA, Baylin SB, Herman JG . Hypermethylation of the DAP-Kinase CpG island is a common alteration in B-cell malignancies. Blood 1999; 93: 4347\u20134353.","journal-title":"Blood"},{"key":"BF2403060_CR17","first-page":"837","volume":"57","author":"JG Herman","year":"1997","unstructured":"Herman JG, Civin CI, Issa JP, Collector MI, Sharkis SJ, Baylin SB . Distinct patterns of inactivation of p15-ink4b and p16-ink4a characterize the major types of hematological malignancies. Cancer Res 1997; 57: 837\u2013841.","journal-title":"Cancer Res"},{"key":"BF2403060_CR18","first-page":"4243","volume":"6","author":"PG Corn","year":"2000","unstructured":"Corn PG, Smith BD, Ruckdeschel ES, Douglas D, Baylin SB, Herman JG . E-cadherin expression is silenced by 5\u2019CpG island methylation in acute leukemia. Clin Cancer Res 2000; 6: 4243\u20134248.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR19","first-page":"1113","volume":"94","author":"S Kawano","year":"1999","unstructured":"Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H et al. Loss of p73 gene expression in leukemias\/lymphomas due to hypermethylation. Blood 1999; 94: 1113\u20131120.","journal-title":"Blood"},{"key":"BF2403060_CR20","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00282-999-0019-5","volume":"41","author":"X Thomas","year":"1999","unstructured":"Thomas X, Teillon MH, Belhabri A, Rimokh R, Fiere D, Magaud JP et al. Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and during complete remission. Hematol Cell Ther 1999; 41: 19\u201326.","journal-title":"Hematol Cell Ther"},{"key":"BF2403060_CR21","first-page":"3730","volume":"59","author":"JR Melki","year":"1999","unstructured":"Melki JR, Vincent PC, Clark SJ . Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia. Cancer Res 1999; 59: 3730\u20133740.","journal-title":"Cancer Res"},{"key":"BF2403060_CR22","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1182\/blood.V97.9.2823","volume":"97","author":"M Toyota","year":"2001","unstructured":"Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP . Methylation profiling in acute myeloid leukemia. Blood 2001; 97: 2823\u20132829.","journal-title":"Blood"},{"key":"BF2403060_CR23","first-page":"2217","volume":"8","author":"G Garcia-Manero","year":"2002","unstructured":"Garcia-Manero G, Daniel J, Smith TL, Kornblau SM, Lee M-S, Kantarjian HM et al. DNA methylation of multiple promoter-associated CpG islands in adult acute lymphoblastic leukemia. Clin Cancer Res 2002; 8: 2217\u20132224.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR24","first-page":"1897","volume":"8","author":"G Garcia-Manero","year":"2002","unstructured":"Garcia-Manero G, Bueso-Ramos C, Daniel J, Williamson J, Kantarjian HM, Issa JP . DNA methylation patterns at relapse in adult acute lymphocytic leukemia. Clin Cancer Res 2002; 8: 1897\u20131903.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR25","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1182\/blood.V99.7.2291","volume":"99","author":"J Roman-Gomez","year":"2002","unstructured":"Roman-Gomez J, Castillejo JA, Jimenez A, Gonzalez MG, Moreno F, Rodriguez MC et al. CpG island hypermethylation is associated with transcriptional silencing of the p21(CIP1\/WAF1\/SDI1) gene and confers poor prognosis in acute lymphoblastic leukemia. Blood 2002; 99: 2291\u20132296.","journal-title":"Blood"},{"key":"BF2403060_CR26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/jnci\/94.1.26","volume":"94","author":"M Esteller","year":"2002","unstructured":"Esteller M, Gaidano G, Goodman SN, Zagonel V, Capello D, Botto B et al. Hypermethylation of the DNA repair gene O6-methyl-guanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. J Natl Cancer Inst 2002; 94: 26\u201332.","journal-title":"J Natl Cancer Inst"},{"key":"BF2403060_CR27","first-page":"1043","volume":"60","author":"K Nosaka","year":"2000","unstructured":"Nosaka K, Maeda M, Tamiya S, Sakai T, Mitsuya H, Matsuoka M . Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia. Cancer Res 2000; 60: 1043\u20131048.","journal-title":"Cancer Res"},{"key":"BF2403060_CR28","first-page":"1077","volume":"5","author":"Q Li","year":"1999","unstructured":"Li Q, Kopecky KJ, Mohan A, Willman CL, Appelbaum FR, Weick JK et al. Estrogen receptor methylation is associated with improved survival in adult acute myeloid leukemia. Clin Cancer Res 1999; 5: 1077\u20131084.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR29","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/sj.leu.2401437","volume":"13","author":"M Nakamura","year":"1999","unstructured":"Nakamura M, Sugita K, Inukai T, Goi K, Iijima K, Tezuka T et al. p16\/MTS1\/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q translocation. Leukemia 1999; 13: 884\u2013890.","journal-title":"Leukemia"},{"key":"BF2403060_CR30","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1182\/blood.V93.7.2380","volume":"93","author":"KW Maloney","year":"1999","unstructured":"Maloney KW, McGavran L, Odom LF, Hunger SP . Acquisition of p16(ink4a) and p15(ink4b) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia. Blood 1999; 93: 2380\u20132385.","journal-title":"Blood"},{"key":"BF2403060_CR31","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1182\/blood.V95.6.1942","volume":"95","author":"IHN Wong","year":"2000","unstructured":"Wong IHN, Ng MHL, Huang DP, Lee JCK . Aberrant p15 promoter methylation in adult and childhood acute leukemias of nearly all morphologic subtypes: potential prognostic implications. Blood 2000; 95: 1942\u20131949.","journal-title":"Blood"},{"key":"BF2403060_CR32","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/cncr.11090","volume":"97","author":"G Garcia-Manero","year":"2003","unstructured":"Garcia-Manero G, Jeha S, Daniel J, Williamson J, Albitar M, Kantarjian HM et al. Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia. Cancer 2003; 97: 695\u2013702.","journal-title":"Cancer"},{"key":"BF2403060_CR33","first-page":"3832","volume":"8","author":"AK Siraj","year":"2002","unstructured":"Siraj AK, Ozbek U, Sazawal S, Sirma S, Timson G, Al-Nasser A et al. Pre-clinical validation of a monochrome real-time multiplex assay for translocations in childhood acute lymphoblastic leukemia. Clin Cancer Res 2002; 8: 3832\u20133840.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR34","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1182\/blood.V95.10.3208","volume":"95","author":"Melki JR","year":"2000","unstructured":"Melki JR, Vincent PC, Brown RD, Clark SJ . Hypermethylation of E-cadherin in leukemia. Blood 2000; 95: 3208\u20133213.","journal-title":"Blood"},{"key":"BF2403060_CR35","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/S0002-9440(10)61758-0","volume":"159","author":"DM Bornman","year":"2001","unstructured":"Bornman DM, Mathew S, Alsruhe J, Herman JG, Gabrielson E . Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial from elderly individuals. Am J Pathol 2001; 159: 831\u2013835.","journal-title":"Am J Pathol"},{"key":"BF2403060_CR36","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1182\/blood.V94.5.1773","volume":"94","author":"AS Baur","year":"1999","unstructured":"Baur AS, Shaw P, Burri N, Delacretaz F, Bosman FT, Chaubert P . Frequent methylation silencing of p15-INK4b (MTS2) and p16-INK4a (MTS1) in B-cell and T-cell lymphomas. Blood 1999; 94: 1773\u20131781.","journal-title":"Blood"},{"key":"BF2403060_CR37","first-page":"832","volume":"57","author":"A Batova","year":"1997","unstructured":"Batova A, Diccianni MB, Yu JC, Nobori T, Link MP, Pullen J et al. Frequent and selective methylation of p15 and deletion of both p15 and p16 in T-cell acute lymphoblastic leukemia. Cancer Res 1997; 57: 832\u2013836.","journal-title":"Cancer Res"},{"key":"BF2403060_CR38","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0145-2126(99)00158-7","volume":"24","author":"SX Guo","year":"2000","unstructured":"Guo SX, Taki T, Ohnishi H, Piao HY, Tabuchi K, Bossho F et al. Hypermethylation of p16 and p15 genes and RB protein expression in acute leukemia. Leuk Res 2000; 24: 39\u201346.","journal-title":"Leuk Res"},{"key":"BF2403060_CR39","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/jnci\/94.10.755","volume":"94","author":"L Shen","year":"2002","unstructured":"Shen L, Ahuja N, Shen Y, Habib NA, Toyota M, Rashid A et al. DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst 2002; 94: 755\u2013761.","journal-title":"J Natl Cancer Inst"},{"key":"BF2403060_CR40","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1038\/sj.leu.2401557","volume":"13","author":"T Taniguchi","year":"1999","unstructured":"Taniguchi T, Chikatsu N, Takahashi S, Fujita A, Uchimaru K, Asano S et al. Expression of p16-INK4A and p14-ARF in hematological malignancies. Leukemia 1999; 13: 1760\u20131769.","journal-title":"Leukemia"},{"key":"BF2403060_CR41","doi-asserted-by":"publisher","first-page":"4231","DOI":"10.1038\/sj.onc.1205528","volume":"21","author":"M Hasegawa","year":"2002","unstructured":"Hasegawa M, Nelson HH, Peters E, Ringstrom E, Posner M, Kelsey K . Patterns of gene promoter methylation in squamous cell cancer of the head and neck. Oncogene 2002; 21: 4231\u20134236.","journal-title":"Oncogene"},{"key":"BF2403060_CR42","first-page":"239","volume":"23","author":"M Liu","year":"2002","unstructured":"Liu M, Li R, Hayashi Y, Zhu G, Guo S . Study on abnormal expression of the p73 gene in childhood acute lymphoblastic leukemia. Zhonghua Xue Ye Xue Za Zhi 2002; 23: 239\u2013242.","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"BF2403060_CR43","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/S0140-6736(00)04501-3","volume":"357","author":"E Evron","year":"2001","unstructured":"Evron E, Dooley WC, Umbricht CB, Rosenthal D, Sacchi N, Gabrielson E et al. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet 2001; 357: 1335\u20131336.","journal-title":"Lancet"},{"key":"BF2403060_CR44","first-page":"433","volume":"8","author":"TS Wong","year":"2002","unstructured":"Wong TS, Chang HW, Tang KC, Wei WI, Kwong DLW, Sham JST et al. High frequency of promoter hypermethylation of the death-associated protein kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients. Clin Cancer Res 2002; 8: 433\u2013437.","journal-title":"Clin Cancer Res"},{"key":"BF2403060_CR45","first-page":"464","volume":"8","author":"MWY Chan","year":"2002","unstructured":"Chan MWY, Chan LW, Tang NLS, Tong JHM, Lo KW, Lee TL et al. Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin Cancer Res 2002; 8: 464\u2013470.","journal-title":"Clin Cancer Res"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/2403060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/2403060","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/2403060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T01:54:58Z","timestamp":1648778098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/2403060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,1]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2003,9,1]]}},"alternative-id":["BF2403060"],"URL":"https:\/\/doi.org\/10.1038\/sj.leu.2403060","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,1]]},"assertion":[{"value":"27 January 2003","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2003","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2003","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}