{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:51:59Z","timestamp":1772805119110,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,8,20]],"date-time":"2003-08-20T00:00:00Z","timestamp":1061337600000},"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":[[2003,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The clinical relevance of mutations of the <jats:italic>FMS<\/jats:italic>\u2010like tyrosine kinase 3 (<jats:italic>FLT3<\/jats:italic>) gene in specific cytogenetic subgroups is not clear. The authors examined internal tandem duplication (ITD) and Asp835 mutations of <jats:italic>FLT3<\/jats:italic> in patients with acute promyelocytic leukemia (APL) to determine the incidence of these mutations and to analyze the results for correlations with clinicohematologic features and outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Bone marrow samples from 107 patients with APL were analyzed. Isoforms of <jats:italic>PML\u2010RAR\u03b1<\/jats:italic> were identified using a reverse transcription\u2013polymerase chain reaction assay. A standard polymerase chain reaction (PCR) assay was used to detect <jats:italic>FLT3<\/jats:italic>\/ITD mutations. Asp835 mutations were analyzed by PCR amplification of exon 20 followed by <jats:italic>Eco<\/jats:italic>RV digestion. All aberrant PCR products subsequently were sequenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Twenty\u2010two patients had <jats:italic>FLT3<\/jats:italic>\/ITD mutations: 9 of 63 patients with L\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>, 13 of 34 patients with S\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>, and 0 of 10 patients with V\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.005). The incidence of <jats:italic>FLT3<\/jats:italic>\/ITD mutations was significantly higher in patients with S\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic> than in patients with L\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic> or V\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>. Twenty patients had Asp835 mutations (L\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>: <jats:italic>n<\/jats:italic> = 11; S\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>: <jats:italic>n<\/jats:italic> = 8; V\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic>: <jats:italic>n<\/jats:italic> = 1). The frequency of Asp835 mutations was not significantly different among patients with different <jats:italic>PML\/RAR\u03b1<\/jats:italic> isoforms (<jats:italic>P<\/jats:italic> = 0.582). Three patients had both ITD and Asp835 mutations. The microgranular variant (M3v) form of leukemia was found to be associated with a higher frequency of ITD (<jats:italic>P<\/jats:italic> = 0.002) but not with a higher frequency of Asp835 mutations (<jats:italic>P<\/jats:italic> = 1.000); analysis of clinicohematologic variables revealed no significant differences in <jats:italic>FLT3<\/jats:italic> mutation incidence among other patient subgroups. There was no significant difference in complete remission rate, overall survival, or event\u2010free survival between patients with ITDs and those without ITDs or between patients with Asp835 mutations and those without Asp835 mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The current study found that ITD or Asp835 mutations of the <jats:italic>FLT3<\/jats:italic> gene were present in 36.4% of patients with APL; however, these mutations had no prognostic impact. <jats:italic>FLT3<\/jats:italic>\/ITD frequently was associated with S\u2010type <jats:italic>PML\/RAR\u03b1<\/jats:italic> and with the M3v form of leukemia. Cancer 2003;98:1206\u201316. \u00a9 2003 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.11636<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.11636","type":"journal-article","created":{"date-parts":[[2003,9,10]],"date-time":"2003-09-10T09:35:52Z","timestamp":1063186552000},"page":"1206-1216","source":"Crossref","is-referenced-by-count":63,"title":["Internal tandem duplication and Asp835 mutations of the <i>FMS\u2010<\/i>like tyrosine kinase 3 (<i>FLT3<\/i>) gene in acute promyelocytic leukemia"],"prefix":"10.1002","volume":"98","author":[{"given":"Lee\u2010Yung","family":"Shih","sequence":"first","affiliation":[]},{"given":"Ming\u2010Chung","family":"Kuo","sequence":"additional","affiliation":[]},{"given":"Der\u2010Cherng","family":"Liang","sequence":"additional","affiliation":[]},{"given":"Chein\u2010Fuang","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Tung\u2010Liang","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Jin\u2010Hou","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Po\u2010Nan","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Po","family":"Dunn","sequence":"additional","affiliation":[]},{"given":"Chang\u2010Liang","family":"Lai","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2003,8,20]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"173","article-title":"Close physical linkage of the FLT1 and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse","volume":"8","author":"Rosnet O","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1110.1110"},{"key":"e_1_2_6_4_2","first-page":"1911","article-title":"Internal tandem duplication of the flt3 gene found in acute myeloid leukemia","volume":"10","author":"Nakao M","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_6_5_2","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_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401731"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1752"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4326"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.1.59"},{"key":"e_1_2_6_10_2","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_6_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.8.2434"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02850.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401130"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01831.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3907"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203354"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401905"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400756"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402723"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0195"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.1254"},{"key":"e_1_2_6_22_2","first-page":"1296","article-title":"Molecular analysis of the PML\/RAR alpha chimeric gene in pediatric acute promyelocytic leukemia","volume":"10","author":"Kane JR","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_6_23_2","unstructured":"National Center for Biotechnology Information. GenBank [database online]. Available from URL:http:\/\/www.ncbi.nlm.nih.gov\/Genbank\/"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122233699"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.4.1192"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.1.78"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.2.483"},{"key":"e_1_2_6_28_2","first-page":"1247","article-title":"Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups","volume":"96","author":"Sanz MA","year":"2000","journal-title":"Blood"},{"key":"e_1_2_6_29_2","first-page":"1014","article-title":"Molecular remission in PML\/RAR alpha\u2010positive acute promyelocytic leukemia by combined all\u2010trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano\u2010Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups","volume":"90","author":"Mandelli F","year":"1997","journal-title":"Blood"},{"key":"e_1_2_6_30_2","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1182\/blood.V84.11.3843.bloodjournal84113843","article-title":", et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low\u2010dose chemotherapy, PML\/RAR\u2010alpha isoform, and CD13 expression in patients treated with all\u2010trans retinoic acid","volume":"84","author":"Vahdat L","year":"1994","journal-title":"Blood"},{"key":"e_1_2_6_31_2","first-page":"1478","article-title":"Isoforms of PML\u2010retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all\u2010trans retinoic acid. 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