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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 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 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 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. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis Brian V. Balgobind1,*, Pieter Van Vlierberghe1,*, Ans M. W. van den Ouweland2, H. Berna Beverloo2, Joan N. R. Terlouw-Kromosoeto2, Elisabeth R. van Wering3, Dirk Reinhardt4, Martin Horstmann5, Gertjan J. L. Kaspers6, Rob Pieters1, C. Michel Zwaan1, Marry M. Van den Heuvel-Eibrink1,, and Jules P. P. Meijerink1, 1 Department of Pediatric Oncology/Hematology, Erasmus MC / Sophia Children's Hospital, Rotterdam, The Netherlands; 2 Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands; 3 Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands; 4 Acute Myeloid Leukemia–Berlin-Frankfurt-Munster (AML-BFM) Study Group, Hannover, Germany; 5 German Co-operative study group for childhood acute lymphoblastic leukemia (COALL), Hamburg, Germany; 6 Department of Pediatric Oncology/Hematology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic hybridization–based screening of 103 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged AML, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. 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 toward the development of leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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