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Blood, 1 August 2007, Vol. 110, No. 3, pp. 1022-1024. Prepublished online as a Blood First Edition Paper on May 2, 2007; DOI 10.1182/blood-2006-12-061176. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-12-061176v1 110/3/1022    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 Citing Articles via Google Scholar Google Scholar Articles by Caligiuri, M. A. Articles by Whitman, S. P. Search for Related Content PubMed PubMed Citation Articles by Caligiuri, M. A. Articles by Whitman, S. P. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia Michael A. Caligiuri1,4, Roger Briesewitz2,5, Jianhua Yu3, Lisheng Wang5, Min Wei2, Kristy J. Arnoczky1, Trent B. Marburger4, Jing Wen2, Danilo Perrotti2,3, Clara D. Bloomfield2,4, and Susan P. Whitman2,4 1 Integrated Biomedical Graduate Program, 2 The Ohio State University Comprehensive Cancer Center, 3 Department of Molecular Biology, Immunology and Medical Genetics, 4 Department of Internal Medicine, Division of Hematology-Oncology, 5 Department of Pharmacology, The Ohio State University, Columbus The CBL ubiquitin ligase targets a variety of activated tyrosine kinases (TKs) for degradation. Many TKs are mutationally or autocrine activated and/or often overexpressed at the mRNA and protein levels in acute leukemias. We hypothesized that CBL is mutated in patients with acute myeloid leukemia (AML). Four of 12 patients and the MOLM-13 cell line harbored c-CBL mutations, either RNA splicing mutations, missense mutations, or a nucleotide insertion. Additionally, 1 of the 12 patients harbored a missense mutation in the related CBL-b gene. Each c-CBL mutation involves the structurally important -helix within the linker region, while the mutation in CBL-b was located in the Ub-E2 protein-binding RING finger. Short-interfering RNA knockdown of mutant c-CBL present in MOLM-13 cells was growth inhibitory. In summary, novel mutations in c-CBL and CBL-b have been identified in human AML and may represent potential targets for novel therapeutics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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