-
- Zhifu Xiang
- Departments of Medicine and
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- Yu Zhao
- Departments of Medicine and
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- Vesselin Mitaksov
- Pathology and Immunology,
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- Daved H. Fremont
- Pathology and Immunology,
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- Yumi Kasai
- Genome Sequencing Center,
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- AnnaLynn Molitoris
- Departments of Medicine and
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- Rhonda E. Ries
- Departments of Medicine and
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- Tracie L. Miner
- Genome Sequencing Center,
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- Michael D. McLellan
- Genome Sequencing Center,
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- John F. DiPersio
- Departments of Medicine and
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- Daniel C. Link
- Departments of Medicine and
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- Jacqueline E. Payton
- Departments of Medicine and
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- Timothy A. Graubert
- Departments of Medicine and
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- Mark Watson
- Pathology and Immunology,
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- William Shannon
- Division of Biostatistics, and
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- Sharon E. Heath
- Departments of Medicine and
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- Rakesh Nagarajan
- Pathology and Immunology,
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- Elaine R. Mardis
- Genome Sequencing Center,
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- Richard K. Wilson
- Genome Sequencing Center,
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- Timothy J. Ley
- Departments of Medicine and
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- Michael H. Tomasson
- Departments of Medicine and
書誌事項
- 公開日
- 2008-05-01
- DOI
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- 10.1182/blood-2007-05-090308
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>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 resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with 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.</jats:p>
収録刊行物
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- Blood
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Blood 111 (9), 4809-4812, 2008-05-01
American Society of Hematology