SEARCH:   Advanced

Blood, 15 April 2008, Vol. 111, No. 8, pp. 4322-4328. Prepublished online as a Blood First Edition Paper on January 2, 2008; DOI 10.1182/blood-2007-06-095075. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-06-095075v1 111/8/4322    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 Balgobind, B. V. Articles by Meijerink, J. P.P. Search for Related Content PubMed PubMed Citation Articles by Balgobind, B. V. Articles by Meijerink, J. P.P. Social Bookmarking                   What's this? Next Article  Submitted June 12, 2007 Accepted December 16, 2007 Leukemia associated NF1 inactivation in pediatric T-ALL and AML patients lacking evidence for neurofibromatosis Brian V. Balgobind, Pieter Van Vlierberghe, Ans M.W. van den Ouweland, H. Berna Beverloo, Joan N.R. Terlouw-Kromosoeto, Elisabeth R. van Wering, Dirk Reinhardt, Martin Horstmann, Gertjan J. L. Kaspers, Rob Pieters, C. Michel Zwaan, Marry M. Van den Heuvel-Eibrink, and Jules P.P. Meijerink* Department of Pediatric Oncology/Hematology, Erasmus MC / Sophia Children's Hospital, Rotterdam, Netherlands Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands Dutch Childhood Oncology Group (DCOG), The Hague, Netherlands AML-BFM Study Group, Hannover, Germany German Co-operative study group for childhood acute lymphoblastic leukemia (COALL), Hamburg, Germany Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, Netherlands * Corresponding author; email: j.meijerink{at}erasmusmc.nl. Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. NF1 patients have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression towards acute myeloid leukemia (AML). In an oligo array-comparative genomic hybridization based screening of 103 pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 MLL rearranged AML patients, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 T-ALL and 2 MLL rearranged AML patients. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, our patients lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumor-suppressor gene in cancer. In addition, NF1 inactivation was confirmed at the RNA expression level in 3 patients tested. Since the NF1 protein is a negative regulator of the RAS pathway (RAS-GTPase activating protein), homozygous NF1 inactivation represent a novel type-I mutation in pediatric MLL rearranged AML and T-ALL with a predicted frequency that is less than 10%. NF1 inactivation may provide an additional proliferative signal towards the development of leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, M. Zimmermann, B. V. Balgobind, S. T. C. J. M. Arentsen-Peters, M. Alders, A. Willasch, G. J. L. Kaspers, J. Trka, A. Baruchel, et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia Blood, June 4, 2009; 113(23): 5951 - 5960. [Abstract] [Full Text] [PDF] H Kehrer-Sawatzki and D N Cooper Mosaicism in sporadic neurofibromatosis type 1: variations on a theme common to other hereditary cancer syndromes? J. Med. Genet., October 1, 2008; 45(10): 622 - 631. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020