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Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2003-01-0137. This Article Full Text (PDF) All Versions of this Article: 2003-01-0137v1 102/4/1474    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 Meshinchi, S. Articles by Radich, J. P Search for Related Content PubMed PubMed Citation Articles by Meshinchi, S. Articles by Radich, J. P Social Bookmarking                   What's this? Submitted January 15, 2003 Accepted April 4, 2003 Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia Soheil Meshinchi*, Derek L Stirewalt, Todd A Alonzo, Quangeng Zhang, David A Sweetser, William G Woods, Irwin D Bernstein, Robert J Arceci, and Jerald P Radich Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Childrens Oncology Group, Arcadia, CA, USA University of Southern California Keck School of Medicine, Los Angeles, CA, USA; Department of Pediatrics and Oncology, Emory University, Atlanta, GA, USA; Department of Pediatric Oncology, Johns Hopkins Medical Institute, Baltimore, MD, USA * Corresponding author; email: smeshinc{at}fhcrc.org. Activating mutations of receptor tyrosine kinases (RTKs) and their downstream affectors are common in AML. We performed mutational analysis of FLT3, c-kit, c-fms, VEGF receptors (Flt-1, KDR) and ras genes in a group of 91 pediatric AML patients treated on Children's Cancer Group clinical trial CCG-2891. Forty-six percent of patients had activating mutations of FLT3 (24.5%), c-kit (3%) or ras (21%) genes. Mutation-positive patients had a higher median diagnostic WBC (71,450 vs. 19,600/mm3; p=0.005) and lower complete remission rate (55% vs. 76%; p=0.046) than mutation-negative patients. The Kaplan-Meier estimate of overall survival (OS) for patients with and without an activating mutation was 34% vs. 57%, respectively (p=0.035). However, within this group, patients with FLT3/ALM had good outcomes (OS 86%). Exclusion of the FLT3/ALM from analysis decreased the OS for the remaining mutation-positive patients to 26% (p=0.003). Ten of the 23 mutation-positive and 11/34 mutation-negative patients received an allogeneic bone marrow transplantation (BMT) in first CR. In the mutation-positive group, the disease-free survival (DFS) for the allogeneic BMT recipients was 72% vs. 23% for the 13 patients who received chemotherapy or autologous BMT (p=0.01). DFS for the mutation-free patients with and without allogeneic BMT was 55% and 40%, respectively (p=0.38). Activating mutations in the RTK/ras signaling pathway are common in pediatric AML, and their presence may identify a population at higher risk of poor outcome who may benefit from allogeneic BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Fuster, E. Barragan, P. Bolufer, J. Cervera, M. J. Larrayoz, A. Jimenez-Velasco, J. Martinez-Lopez, A. Valencia, F. Moscardo, and M. A. Sanz Rapid Detection of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia Using High-Resolution Melting Analysis J. Mol. Diagn., September 1, 2009; 11(5): 458 - 463. [Abstract] [Full Text] [PDF] S. Meshinchi and F. R. 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