SEARCH:   Advanced

Blood, 11 June 2009, Vol. 113, No. 24, pp. 6182-6192. Prepublished online as a Blood First Edition Paper on April 22, 2009; DOI 10.1182/blood-2008-12-194548. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-12-194548v1 113/24/6182    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 Grand, F. H. Articles by Cross, N. C. P. PubMed PubMed Citation Articles by Grand, F. H. Articles by Cross, N. C. P. Related Collections Free Research Articles Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms Francis H. Grand1,*, Claire E. Hidalgo-Curtis1,*, Thomas Ernst1, Katerina Zoi2, Christine Zoi2, Carolann McGuire3, Sebastian Kreil1, Amy Jones1, Joannah Score1, Georgia Metzgeroth4, David Oscier5, Andrew Hall6, Christian Brandts7, Hubert Serve7, Andreas Reiter4, Andrew J. Chase1, and Nicholas C. P. Cross1 1 Wessex Regional Genetics Laboratory, Salisbury, and Human Genetics Division, School of Medicine, University of Southampton, Southampton, United Kingdom; 2 Haematology Research Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece; 3 Inflammation, Infection and Repair Division, School of Medicine, University of Southampton, Southampton, United Kingdom; 4 III Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany; 5 Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom; 6 Northern Institute for Cancer Research, Newcastle upon Tyne, United Kingdom; and 7 Department of Medicine, Hematology & Oncology, University of Frankfurt, Frankfurt, Germany Recent evidence has demonstrated that acquired uniparental disomy (aUPD) is a novel mechanism by which pathogenetic mutations in cancer may be reduced to homozygosity. To help identify novel mutations in myeloproliferative neoplasms (MPNs), we performed a genome-wide single nucleotide polymorphism (SNP) screen to identify aUPD in 58 patients with atypical chronic myeloid leukemia (aCML; n = 30), JAK2 mutation–negative myelofibrosis (MF; n = 18), or JAK2 mutation–negative polycythemia vera (PV; n = 10). Stretches of homozygous, copy neutral SNP calls greater than 20Mb were seen in 10 (33%) aCML and 1 (6%) MF, but were absent in PV. In total, 7 different chromosomes were involved with 7q and 11q each affected in 10% of aCML cases. CBL mutations were identified in all 3 cases with 11q aUPD and analysis of 574 additional MPNs revealed a total of 27 CBL variants in 26 patients with aCML, myelofibrosis or chronic myelomonocytic leukemia. Most variants were missense substitutions in the RING or linker domains that abrogated CBL ubiquitin ligase activity and conferred a proliferative advantage to 32D cells overexpressing FLT3. We conclude that acquired, transforming CBL mutations are a novel and widespread pathogenetic abnormality in morphologically related, clinically aggressive MPNs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. R. McKeller, R. S. Robetorye, P. L. M. Dahia, and R. C. T. Aguiar Integrity of the CBL gene in mature B-cell malignancies Blood, November 5, 2009; 114(19): 4321 - 4322. [Full Text] [PDF] S. R. Bandi, C. Brandts, M. Rensinghoff, R. Grundler, L. Tickenbrock, G. Kohler, J. Duyster, W. E. Berdel, C. Muller-Tidow, H. Serve, et al. E3 ligase-defective Cbl mutants lead to a generalized mastocytosis and myeloproliferative disease Blood, November 5, 2009; 114(19): 4197 - 4208. [Abstract] [Full Text] [PDF] M. L. Loh, D. S. Sakai, C. Flotho, M. Kang, M. Fliegauf, S. Archambeault, C. G. Mullighan, L. Chen, E. Bergstraesser, C. E. Bueso-Ramos, et al. Mutations in CBL occur frequently in juvenile myelomonocytic leukemia Blood, August 27, 2009; 114(9): 1859 - 1863. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020