Linked Life Data

20404132

Source:http://linkedlifedata.com/resource/pubmed/id/20404132

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-8-13
pubmed:abstractText
Dysregulated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling due to activation of tyrosine kinases is a common feature of myeloid malignancies. Here we report the first human disease-related mutations in the adaptor protein LNK, a negative regulator of JAK-STAT signaling, in 2 patients with JAK2 V617F-negative myeloproliferative neoplasms (MPNs). One patient exhibited a 5 base-pair deletion and missense mutation leading to a premature stop codon and loss of the pleckstrin homology (PH) and Src homology 2 (SH2) domains. A second patient had a missense mutation (E208Q) in the PH domain. BaF3-MPL cells transduced with these LNK mutants displayed augmented and sustained thrombopoietin-dependent growth and signaling. Primary samples from MPN patients bearing LNK mutations exhibited aberrant JAK-STAT activation, and cytokine-responsive CD34(+) early progenitors were abnormally abundant in both patients. These findings indicate that JAK-STAT activation due to loss of LNK negative feedback regulation is a novel mechanism of MPN pathogenesis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-11752654, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-11805142, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-12070287, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15260991, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15337790, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15705783, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15781101, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15793561, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15837627, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-15858187, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16332975, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16603627, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16834459, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16868251, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16871275, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-16923108, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-17267906, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-17376889, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-17693582, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-18618018, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-18835035, http://linkedlifedata.com/resource/pubmed/commentcorrection/20404132-20705765
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
988-92
pubmed:dateRevised
2011-8-25
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms.
pubmed:affiliation
Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr., Stanford, CA 94305-5821, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural