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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4809-4812. Prepublished online as a Blood First Edition Paper on December 26, 2007; DOI 10.1182/blood-2007-05-090308. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-05-090308v1 111/9/4809    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 Xiang, Z. Articles by Tomasson, M. H Search for Related Content PubMed PubMed Citation Articles by Xiang, Z. Articles by Tomasson, M. H Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 14, 2007 Accepted November 9, 2007 Identification of somatic JAK1 mutations in patients with acute myeloid leukemia Zhifu Xiang, Yu Zhao, Vesselin Mitaksov, Daved H Fremont, Yumi Kasai, AnnaLynn Molitoris, Rhonda E Ries, Tracie L Miner, Michael D McLellan, John F DiPersio, Daniel C Link, Jacqueline E Payton, Timothy A Graubert, Mark Watson, William Shannon, Sharon E Heath, Rakesh Naggarajan, Elaine R Mardis, Richard K Wilson, Timothy J Ley, and Michael H Tomasson* Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, United States Genome Sequencing Center, Washington University School of Medicine, Saint Louis, MO, United States Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, United States Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States Department of Genetics, Washington University School of Medicine, Saint Louis, MO, United States * Corresponding author; email: tomasson{at}wustl.edu. Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic re-sequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified two novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in two separate patients and confirmed these by re-sequencing germline DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared to wild-type JAK1, JAK1T478S and JAK1V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease modifying mutations in AML pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hitchhikers' guide to the leukemia genome Nicholas C. P. Cross Blood 2008 111: 4428-4429. [Full Text] [PDF] This article has been cited by other articles: M. H. Tomasson, Z. Xiang, R. Walgren, Y. Zhao, Y. Kasai, T. Miner, R. E. Ries, O. Lubman, D. H. Fremont, M. D. McLellan, et al. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia Blood, May 1, 2008; 111(9): 4797 - 4808. [Abstract] [Full Text] [PDF]

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