Year: 2007
Type: article
Study design: Observational Study
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.
Source: Blood
Authors: 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
Institutions: Pediatrics and Genetics, Washington University in St. Louis
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2032532485