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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1308-1316. Prepublished online as a Blood First Edition Paper on May 7, 2007; DOI 10.1182/blood-2007-02-072595. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-072595v1 110/4/1308    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 Dicker, F. Articles by Schnittger, S. Search for Related Content PubMed PubMed Citation Articles by Dicker, F. Articles by Schnittger, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 5, 2007 Accepted May 4, 2007 Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3-expression in acute myeloid leukemia Frank Dicker*, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach, and Susanne Schnittger MLL, Munich Leukemia Laboratory, Munich, Germany * Corresponding author; email: frank.dicker{at}mll-online.com. AML1/RUNX1 is implicated in leukemogenesis on the basis of the AML1-ETO fusion transcript as well as somatic mutations in its DNA-binding domain. Somatic mutations in RUNX1 are preferentially detected in AML M0, myeloid malignancies with acquired trisomy 21 and certain MDS cases. By correlating the presence of RUNX1-mutations with cytogenetic and molecular aberration in a large cohort of AML M0 (n=90) at diagnosis, we detected RUNX1-mutations in 46% of cases with all trisomy 13 cases (n=18) being affected. No mutations of NRAS or KIT were detected in the RUNX1-mutated group and FLT3-mutations were equally distributed between RUNX1-mutated and unmutated samples. Likewise, a high incidence of RUNX1-mutations (80%) was detected in cases with trisomy 13 from other FAB subgroups (n=20). As FLT3 is localized on chromosome 13, we hypothesized that RUNX1-mutations might cooperate with trisomy 13 in leukemogenesis by increasing FLT3-transcript levels. Quantitation of FLT3-transcript levels revealed a highly significant (p < 0.001) about five-fold increase in AML with RUNX1-mutations and trisomy 13 compared to samples without trisomy 13. The results of the present study indicate that in the absence of FLT3 mutations, FLT3-overexpression might be a mechanism for FLT3-activation, which cooperates with RUNX1-mutations in leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Roche-Lestienne, L. Deluche, S. Corm, I. Tigaud, S. Joha, N. Philippe, S. Geffroy, J.-L. Lai, F.-E. Nicolini, C. Preudhomme, et al. RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance Blood, April 1, 2008; 111(7): 3735 - 3741. [Abstract] [Full Text] [PDF]

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