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This Article Full Text Full Text (PDF) Erratum (v98,p924) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Stirewalt, D. L. Articles by Radich, J. P. Search for Related Content PubMed PubMed Citation Articles by Stirewalt, D. L. Articles by Radich, J. P. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2001, Vol. 97, No. 11, pp. 3589-3595 NEOPLASIA FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia Derek L. Stirewalt, Kenneth J. Kopecky, Soheil Meshinchi, Frederick R. Appelbaum, Marilyn L. Slovak, Cheryl L. Willman, and Jerald P. Radich From the Fred Hutchinson Cancer Research Center, Seattle, Washington. The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for FLT3, RAS, and TP53 mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the FLT3 (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. FLT3 ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with FLT3 ITDs also had a RAS mutation, indicating a significant negative association between FLT3 and RAS mutations (P = .0013). Most TP53 mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. FLT3 and RAS mutations were not associated with inferior clinical outcomes, but TP53 mutations were associated with a worse overall survival (median 1 versus 8 months, P = .0007). These results indicate that mutations in FLT3, RAS, or TP53 are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Fukuda, P. Singh, A. Moh, M. Abe, E. M. Conway, H. S. Boswell, S. Yamaguchi, X.-Y. Fu, and L. M. Pelus Survivin mediates aberrant hematopoietic progenitor cell proliferation and acute leukemia in mice induced by internal tandem duplication of Flt3 Blood, July 9, 2009; 114(2): 394 - 403. [Abstract] [Full Text] [PDF] S. Meshinchi and F. R. Appelbaum Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia Clin. Cancer Res., July 1, 2009; 15(13): 4263 - 4269. [Abstract] [Full Text] [PDF] A. Nordigarden, M. Kraft, P. Eliasson, V. Labi, E. W.-F. Lam, A. Villunger, and J.-I. 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