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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 4, 2006 Accepted April 30, 2007 Novel c-CBL and CBL-B ubiquitin ligase mutations in human acute myeloid leukemia Michael A. Caligiuri, Roger Briesewitz, Jianhua Yu, Lisheng Wang, Min Wei, Kristy J. Arnoczky, Trent B. Marburger, Jing Wen, Danilo Perrotti, Clara D. Bloomfield, and Susan P Whitman* Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH Dept of Molecular Biology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH Department of Pharmacology, The Ohio State University, Columbus, OH Department of Internal Medicine, The Ohio State University, Columbus, OH * Corresponding author; email: susan.whitman{at}osumc.edu. The CBL ubiquitin ligase targets a variety of activated tyrosine kinases (TK) for degradation. Many TKs are mutationally or autocrine-activated and/or often over-expressed 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, one 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 BL-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? Related Article in Blood Online: Partners in AML: Flt3 and c-Cbl Wallace Y. Langdon Blood 2007 110: 793-794. [Full Text] [PDF] 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. 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