{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:17:36Z","timestamp":1790914656166,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,7,12]],"date-time":"2004-07-12T00:00:00Z","timestamp":1089590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The prognostic significance of internal tandem duplication (ITD) of the <jats:italic>fms<\/jats:italic>\u2010like tyrosine kinase 3 gene (<jats:italic>FLT3<\/jats:italic>) for patients with myelodysplastic syndrome (MDS) is not clearly defined. In the current study, the authors sought to assess the value of <jats:italic>FLT3<\/jats:italic>\/ITD mutation status as a prognostic genetic marker for patients with MDS.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:italic>FLT3<\/jats:italic>\/ITD mutation status was evaluated by performing DNA polymerase chain reaction assays on 198 bone marrow samples obtained from patients with MDS at initial diagnosis. All aberrant products were sequenced, and GeneScan analysis was performed to measure <jats:italic>FLT3<\/jats:italic>\/ITD mutant levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Five patients (2.5%)\u20142 of the 99 patients who had refractory anemia with excess blasts and 3 of the 51 patients who had chronic myelomonocytic leukemia\u2014had <jats:italic>FLT3<\/jats:italic>\/ITD mutations. <jats:italic>FLT3<\/jats:italic>\/ITD was not observed in any of the 48 patients who had refractory anemia (with or without ringed sideroblasts). There was no significant difference in clinicohematologic characteristics, cytogenetic characteristics, or International Prognostic Scoring System score between the <jats:italic>FLT3<\/jats:italic>\/ITD\u2010positive group and the <jats:italic>FLT3<\/jats:italic>\/ITD\u2010negative group. Four of the 5 patients carrying the <jats:italic>FLT3<\/jats:italic>\/ITD mutation experienced progression of disease to acute myeloid leukemia (AML), compared with 70 of the 193 patients who did not have <jats:italic>FLT3<\/jats:italic>\/ITD (<jats:italic>P<\/jats:italic> = 0.066). In addition, progression to AML was more rapid in patients with <jats:italic>FLT3<\/jats:italic>\/ITD\u2010positive disease than in patients with <jats:italic>FLT3<\/jats:italic>\/ITD\u2010negative disease (mean \u00b1 standard error, 3.0 \u00b1 0.5 months vs. 62.8 \u00b1 5.6 months; <jats:italic>P<\/jats:italic> &lt; 0.0001). Patients with <jats:italic>FLT3<\/jats:italic>\/ITD\u2010positive disease also had significantly shorter survival compared with patients who had <jats:italic>FLT3<\/jats:italic>\/ITD\u2010negative disease (mean \u00b1 standard error, 5.2 \u00b1 1.4 months vs. 33.7 \u00b1 3.1 months; <jats:italic>P<\/jats:italic> &lt; 0.0001). On multivariate analysis, <jats:italic>FLT3<\/jats:italic>\/ITD was identified as an independent predictor of reduced time to development of AML (<jats:italic>P<\/jats:italic> = 0.0001) and reduced overall survival (<jats:italic>P<\/jats:italic> = 0.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The results of the current study demonstrate that <jats:italic>FLT3<\/jats:italic>\/ITD is associated with a high risk of transformation to AML, rapid progression of AML, and poor survival in patients with MDS. Cancer 2004. \u00a9 2004 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20440","type":"journal-article","created":{"date-parts":[[2004,7,12]],"date-time":"2004-07-12T17:05:57Z","timestamp":1089651957000},"page":"989-998","source":"Crossref","is-referenced-by-count":36,"title":["Internal tandem duplication of <i>fms<\/i>\u2010like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome"],"prefix":"10.1002","volume":"101","author":[{"given":"Lee\u2010Yung","family":"Shih","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung\u2010Liang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Nan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Hou","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Chung","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chein\u2010Fuang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,8,18]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"953","article-title":"Myelodysplastic syndromes: natural history and features of prognostic importance","volume":"15","author":"Mufti GJ","year":"1986","journal-title":"Clin Haematol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400934"},{"key":"e_1_2_6_4_2","first-page":"370","article-title":"Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. 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