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.
相似文献