{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:22:33Z","timestamp":1791206553267,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,4,16]],"date-time":"2003-04-16T00:00:00Z","timestamp":1050451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"crossref","award":["70-2210-Eh5"],"award-info":[{"award-number":["70-2210-Eh5"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kompetenznetzwerk Akute and Chronische Leuk\u00e4mien"},{"name":"Bundesministerium f. Bildung und Forschung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Partial tandem duplication (PTD) of the <jats:italic>MLL<\/jats:italic> gene and internal tandem duplication (ITD) of the juxtamembrane region of the <jats:italic>FLT3<\/jats:italic> receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well\u2010defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. <jats:italic>MLL<\/jats:italic> PTD was detected by RT\u2010PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48\/956), whereas <jats:italic>FLT3<\/jats:italic> ITD was detected in 19.2% (184\/956). Sixteen cases were positive for both alterations. The rate of <jats:italic>MLL<\/jats:italic> PTD in <jats:italic>FLT3<\/jats:italic> ITD positive patients was significantly higher than that in <jats:italic>FLT3<\/jats:italic> ITD negative patients [16\/184 (8.7%); 32\/772 (4.1%); <jats:italic>P<\/jats:italic> = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (<jats:italic>MLL<\/jats:italic> PTD 35\/431, <jats:italic>P<\/jats:italic> = 0.004; <jats:italic>FLT3<\/jats:italic> ITD 132\/334, <jats:italic>P<\/jats:italic> &lt; 0.001). When restricted to this subgroup, the rate of <jats:italic>MLL<\/jats:italic> PTD in patients with <jats:italic>FLT3<\/jats:italic> mutations was not significantly increased. No statistically significant differences were detected between patients positive for <jats:italic>MLL<\/jats:italic> PTD and patients negative for <jats:italic>MLL<\/jats:italic> PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease\u2010free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with <jats:italic>FLT3<\/jats:italic> ITD and <jats:italic>MLL<\/jats:italic> PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease\u2010free survival, the results of this study do not unequivocally support the notion that <jats:italic>MLL<\/jats:italic> PTD mutations represent an independent prognostic factor. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10219","type":"journal-article","created":{"date-parts":[[2003,5,16]],"date-time":"2003-05-16T11:32:50Z","timestamp":1053084770000},"page":"237-251","source":"Crossref","is-referenced-by-count":130,"title":["Comparative analysis of <i>MLL<\/i> partial tandem duplication and <i>FLT3<\/i> internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia"],"prefix":"10.1002","volume":"37","author":[{"given":"Christine","family":"Steudel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wermke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schaich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Sch\u00e4kel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Illmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Ehninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Thiede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2000.02317.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400933"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/genetics\/136.3.965","article-title":"Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila","volume":"136","author":"Bomze HM","year":"1994","journal-title":"Genetics"},{"key":"e_1_2_7_5_1","first-page":"370","article-title":"Molecular rearrangement of the ALL\u20101 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations","volume":"54","author":"Caligiuri MA","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_7_6_1","first-page":"1418","article-title":"Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11","volume":"56","author":"Caligiuri MA","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_7_7_1","first-page":"55","article-title":"Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics","volume":"58","author":"Caligiuri MA","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402246"},{"key":"e_1_2_7_10_1","first-page":"1625","article-title":"ALL\u20101 gene rearrangements in acute myeloid leukemia: association with M4\u2013M5 French\u2010American\u2010British classification subtypes and young age","volume":"55","author":"Cimino G","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.20.9677"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1999.01439.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00111-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.09.088"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.4.1192"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01831.x"},{"key":"e_1_2_7_17_1","first-page":"1179","article-title":"Double knockout of the ALL\u20101 gene blocks hematopoietic differentiation in vitro","volume":"56","author":"Fidanza V","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203354"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.5.1799"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.1132"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21979"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400756"},{"key":"e_1_2_7_23_1","first-page":"3074","article-title":"Prognostic implication of FLT3 and N\u2010RAS gene mutations in acute myeloid leukemia","volume":"93","author":"Kiyoi H","year":"1999","journal-title":"Blood"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1752"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0420"},{"key":"e_1_2_7_26_1","volume-title":"ISCN: an international system for human cytogenetic nomenclature","author":"Mitelman F","year":"1995"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3907"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(96)00364-2"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.d01-1748.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.2933107.x"},{"key":"e_1_2_7_31_1","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook J","year":"1989"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02562.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.13.6236"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.5.1728"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401773"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402352"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0195"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(97)00035-X"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4326"},{"key":"e_1_2_7_40_1","first-page":"7233","article-title":"Absence of the wild\u2010type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study","volume":"61","author":"Whitman SP","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1999.01291.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/378505a0"},{"key":"e_1_2_7_43_1","first-page":"774","article-title":"MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype","volume":"10","author":"Yu M","year":"1996","journal-title":"Leukemia"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.10219","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.10219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:46:40Z","timestamp":1696625200000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.10219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,16]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,7]]}},"alternative-id":["10.1002\/gcc.10219"],"URL":"https:\/\/doi.org\/10.1002\/gcc.10219","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,16]]}}}