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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2113-2119. Prepublished online as a Blood First Edition Paper on June 16, 2005June 14, 2005; DOI 10.1182/blood-2005-03-0867. This Article Full Text (PDF) All Versions of this Article: 2005-03-0867v1 2005-03-0867v2 2005-03-0867v3 106/6/2113    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 Bowen, D. T Articles by Linch, D. C Search for Related Content PubMed PubMed Citation Articles by Bowen, D. T Articles by Linch, D. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 2, 2005 Accepted April 9, 2005 RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients < 60 yrs David T Bowen*, Marion E Frew, Robert Hills, Rosemary E Gale, Keith Wheatley, Michael J Groves, Stephen E Langabeer, Panagiotis D Kottaridis, Anthony V Moorman, Alan K Burnett, and David C Linch Division of Pathology and Neuroscience, Ninewells Hospital, University of Dundee, Dundee, United Kingdom University of Birmingham Clinical Trials Unit, Birmingham, United Kingdom Department of Haematology, University College London, London, United Kingdom LRF Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom National Cancer Research Institute Adult Leukemia Working Party and Cardiff University, Cardiff, United Kingdom * Corresponding author; email: d.t.bowen{at}dundee.ac.uk. The pathogenesis of acute myeloid leukemia involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. The RAS pathway has been implicated as a key component of the proliferative drive in AML. We have screened AML patients, predominantly < 60 years old and treated within two clinical trials, for NRAS (n=1106), KRAS (n=739), and HRAS (n=200) hotspot mutations using denaturing high performance liquid chromatography or restriction fragment length polymorphism (RFLP) analysis. NRAS mutations were confirmed in 11% of patients (126/1106) and KRAS mutations in 5% (39/739). No HRAS mutations were detected in 200 randomly selected samples. Codons most frequently mutated were N12 (43%), N13 (21%) and K12 (21%). KRAS mutations were relatively over-represented in FAB type M4 (P< .001). NRAS mutation was over-represented in the t(3;5)(q21~25;q31~q35) subgroup (P< .001) and under-represented in t(15;17)(q22;q21) (P< .001). KRAS mutation was over-represented in inv(16)(p13q22) (P=.004). 23% KRAS mutations were within the inv(16) subgroup. RAS mutation and FLT3 ITD were rarely coexistent (14/768 P< .001). Median percentage of RAS mutant allele assayed by quantitative RFLP analysis was 28% (N12), 19% (N13), 25% (N61) and 21% (K12). RAS mutation did not influence clinical outcome (overall / disease-free survival, complete remission, relapse rate) either for the entire cohort, or within cytogenetic risk groups. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. P.G. Silva, I. Almeida, B. Morolli, G. Brouwer-Mandema, H. Wessels, R. Vossen, H. Vrieling, E. W.A. Marijt, P. J.M. Valk, H. C. Kluin-Nelemans, et al. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia Haematologica, November 1, 2009; 94(11): 1546 - 1554. 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