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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-02-0418. This Article Full Text (PDF) All Versions of this Article: 2003-02-0418v1 103/3/1085    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Taketani, T. Articles by Hayashi, Y. Search for Related Content PubMed PubMed Citation Articles by Taketani, T. Articles by Hayashi, Y. Social Bookmarking                   What's this? Submitted February 7, 2003 Accepted September 7, 2003 FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy Takeshi Taketani, Tomohiko Taki, Kanji Sugita, Yoshiyuki Furuichi, Eiichi Ishii, Ryoji Hanada, Masahiro Tsuchida, Kenichi Sugita, Kohmei Ida, and Yasuhide Hayashi* Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Gunma Children's Medical Center, Gunma, Japan Department of Pediatrics, Shimane Medical University, Shimane, Japan Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan Department of Pediatrics, Saga Medical School, Saga, Japan Division of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan Department of Pediatrics, Ibaraki Children's Hospital, Ibaraki, Japan Division of Hematology, Dokkyo University School of Medicine, Tochigi, Japan * Corresponding author; email: hayashiy-tky{at}umin.ac.jp. Point mutations of D835/I836 of the FLT3 gene have been reported in adult acute myeloid leukemia (AML), but not in pediatric AML or acute lymphoblastic leukemia (ALL). FLT3-D835/I836 mutations were found in 6 (5.4%) of 112 pediatric ALLs more than one year old, and 8 (16.0%) of 50 infant ALLs. Missense mutation was found in 11 patients, 3-bp deletion in 2, and deletion/insertion in one. Remarkably, FLT3-D835/I836 mutations were frequently found in 8 (18.2%) of 44 infant ALL with MLL rearrangements and in 4 (21.5%) of 19 hyperdiploid ALL patients, but not in any patients with TEL-AML1 (n=11), E2A-PBX1 (n=4), or BCR-ABL (n=6) fusion genes more than 1 year of age. Although the infant ALL patients with mutations had a poorer prognosis than those without mutations, pediatric ALL patients more than one year with mutations had a good prognosis. We also found FLT3-D835 mutations in 2 of 11 leukemic cell lines with MLL rearrangements. FLT3 was highly phosphorylated in these cell lines with FLT3-D835 mutations, leading to constitutive activation of downstream targets such as STAT5 without FL stimulation. These results suggested that FLT3-D835/I836 mutations are one of the second genetic events in infant ALL with MLL rearrangements or pediatric ALL with hyperdiploidy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Bueno, P. Catalina, G. J. Melen, R. Montes, L. Sanchez, G. Ligero, J. L. Garcia-Perez, and P. Menendez Etoposide induces MLL rearrangements and other chromosomal abnormalities in human embryonic stem cells Carcinogenesis, September 1, 2009; 30(9): 1628 - 1637. [Abstract] [Full Text] [PDF] M. Case, E. Matheson, L. Minto, R. Hassan, C. J. Harrison, N. Bown, S. Bailey, J. Vormoor, A. G. Hall, and J. A.E. 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