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Blood, 4 June 2009, Vol. 113, No. 23, pp. 5951-5960. Prepublished online as a Blood First Edition Paper on January 26, 2009; DOI 10.1182/blood-2008-09-177949. This Article Full Text Full Text (PDF) Supplemental Appendices and Tables All Versions of this Article: blood-2008-09-177949v1 113/23/5951    most recent 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 Google Scholar Articles by Hollink, I. H. I. M. Articles by Zwaan, C. M. PubMed PubMed Citation Articles by Hollink, I. H. I. M. Articles by Zwaan, C. M. Related Collections Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia Iris H. I. M. Hollink1, Marry M. van den Heuvel-Eibrink1, Martin Zimmermann2, Brian V. Balgobind1, Susan T. C. J. M. Arentsen-Peters1, Marielle Alders3, Andre Willasch4, Gertjan J. L. Kaspers5, Jan Trka6, Andre Baruchel7, Siebold S. N. de Graaf8, Ursula Creutzig9, Rob Pieters1, Dirk Reinhardt2, and C. Michel Zwaan1 1 Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands; 2 AML-BFM Study Group, Department of Pediatric Oncology/Hematology, Medical High School, Hannover, Germany; 3 Clincial Genetics, Academic Medical Center, Amsterdam, The Netherlands; 4 Department of Hematology and Oncology, University Children's Hospital of Frankfurt, Frankfurt, Germany; 5 Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands; 6 Pediatric Haematology/Oncology, Second Medical School, Charles University Prague, Prague, Czech Republic; 7 Hematology, Saint-Louis Hospital, Paris, France; 8 Department of Pediatric Oncology/Hematology, Radboud University Medical Center, Nijmegen, The Netherlands; and 9 AML-BFM Study Group, University Children's Hospital, Münster, Germany Wilms tumor 1 (WT1) mutations have recently been identified in approximately 10% of adult acute myeloid leukemia (AML) with normal cytogenetics (CN-AML) and are associated with poor outcome. Using array-based comparative genome hybridization in pediatric CN-AML samples, we detected a WT1 deletion in one sample. The other WT1 allele was mutated. This prompted us to further investigate the role of WT1 aberrations in childhood AML. Mutations were found in 35 of 298 (12%) diagnostic pediatric AML samples. In 19 of 35 (54%) samples, more than one WT1 aberration was found: 15 samples had 2 different mutations, 2 had a homozygous mutation, and 2 had a mutation plus a WT1 deletion. WT1 mutations clustered significantly in the CN-AML subgroup (22%; P < .001) and were associated with FLT3/ITD (43 vs 17%; P < .001). WT1 mutations conferred an independent poor prognostic significance (WT1 mutated vs wild-type patients: 5-year probability of overall survival [pOS] 35% vs 66%, P = .002; probability of event-free survival 22% vs 46%, P < .001; and cumulative incidence of relapse or regression 70% vs 44%, P < .001). Patients with both a WT1 mutation and a FLT3/ITD had a dismal prognosis (5-year pOS 21%). WT1 mutations occur at a significant rate in childhood AML and are a novel independent poor prognostic marker. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Adding WT1 to childhood AML alphabet soup Patrick Brown Blood 2009 113: 5696-5697. [Full Text] [PDF] This article has been cited by other articles: I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, and C. M. Zwaan CEBPA resembles Roman god Janus Blood, June 25, 2009; 113(26): 6501 - 6502. [Full Text] [PDF] P. Brown Adding WT1 to childhood AML alphabet soup Blood, June 4, 2009; 113(23): 5696 - 5697. [Full Text] [PDF]

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