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 Nagarajan; Elaine R Mardis; Richard K Wilson; Timothy J Ley; Michael H Tomasson

doi:10.1182/blood-2007-05-090308

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Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Journal article

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Peer reviewed

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, …

Blood, Vol.111(9), pp.4809-4812

Neoplasia

05/01/2008

DOI: 10.1182/blood-2007-05-090308

PMCID: PMC2343608

PMID: 18160671

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Abstract

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 , JAK1 T478S , and JAK1 V623A 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.

Neoplasia

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Title: Subtitle: Identification of somatic JAK1 mutations in patients with acute myeloid leukemia
Creators: Zhifu Xiang - Departments of
Yu Zhao - Departments of
Vesselin Mitaksov - Pathology and Immunology
Daved H Fremont - Pathology and Immunology
Yumi Kasai - Genome Sequencing Center
AnnaLynn Molitoris - Departments of
Rhonda E Ries - Departments of
Tracie L Miner - Genome Sequencing Center
Michael D McLellan - Genome Sequencing Center
John F DiPersio - Departments of
Daniel C Link - Departments of
Jacqueline E Payton - Departments of
Timothy A Graubert - Departments of
Mark Watson - Pathology and Immunology
William Shannon - Division of Biostatistics, and
Sharon E Heath - Departments of
Rakesh Nagarajan - Pathology and Immunology
Elaine R Mardis - Genome Sequencing Center
Richard K Wilson - Genome Sequencing Center
Timothy J Ley - Departments of
Michael H Tomasson - Departments of
Resource Type: Journal article
Publication Details: Blood, Vol.111(9), pp.4809-4812
Publisher: American Society of Hematology
Series: Neoplasia
DOI: 10.1182/blood-2007-05-090308
PMID: 18160671
PMCID: PMC2343608
ISSN: 0006-4971
eISSN: 1528-0020
Language: English
Date published: 05/01/2008
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094338302771

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