Linked Life Data

16598306

Source:http://linkedlifedata.com/resource/pubmed/id/16598306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-24
pubmed:abstractText
Signal transducer and activator of transcription (STAT) proteins are phosphorylated and activated by Janus kinases (JAKs). Recently, several groups identified a recurrent somatic point mutation constitutively activating the hematopoietic growth factor receptor-associated JAK2 tyrosine kinase in diverse chronic myeloid disorders - most commonly classic myeloproliferative disorders (MPD), especially polycythemia vera. We hypothesized that the JAK2 V617F mutation might also be present in samples from patients with acute myeloid leukemia (AML), especially erythroleukemia (AML-M6) or megakaryoblastic leukemia (AML-M7), where it might mimic erythropoietin or thrombopoietin signaling. First, we documented STAT3 activation by immunoblotting in AML-M6 and other AML subtypes. Immunoperoxidase staining confirmed phosphorylated STAT3 in malignant myeloblasts (21% of cases, including all AML-M3 samples tested). We then analyzed genomic DNA from 162 AML, 30 B-cell lymphoma, and 10 chronic lymphocytic leukemia (CLL) samples for JAK2 mutations, and assayed a subset for SOCS1 and FLT3 mutations. Janus kinase2 V617F was present in 13/162 AML samples (8%): 10/13 transformed MPD, and three apparent de novo AML (one of 12 AML-M6, one of 24 AML-M7, and one AML-M2 - all mixed clonality). FLT3 mutations were present in 5/32 (16%), while SOCS1 mutations were totally absent. Lymphoproliferative disorder samples were both JAK2 and SOCS1 wild type. Thus, while JAK2 V617F is uncommon in de novo AML and probably does not occur in lymphoid malignancy, unexplained STAT3 activation is common in AML. Janus kinase2 extrinsic regulators and other proteins in the JAK-STAT pathway should be interrogated to explain frequent STAT activation in AML.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
971-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained.
pubmed:affiliation
Mayo Clinic College of Medicine, Rochester, MN, USA. Steensma.david@mayo.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural