Source:http://linkedlifedata.com/resource/pubmed/id/14737077
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2004-2-24
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pubmed:abstractText |
The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, P<0.001). FLT3/ITD(+) patients progressed to AML more rapidly than FLT3/ITD(-) patients (2.5+/-0.5 vs 11.9+/-1.5 months, P=0.114). FLT3/ITD(+) patients had a significantly shorter survival than FLT3/ITD(-) patients (5.6+/-1.3 vs 18.0+/-1.7 months, P=0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (P<0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FLT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/fms-Like Tyrosine Kinase 3
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0887-6924
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
466-75
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14737077-Acute Disease,
pubmed-meshheading:14737077-Bone Marrow,
pubmed-meshheading:14737077-Cell Transformation, Neoplastic,
pubmed-meshheading:14737077-Disease Progression,
pubmed-meshheading:14737077-Female,
pubmed-meshheading:14737077-Genes, ras,
pubmed-meshheading:14737077-Humans,
pubmed-meshheading:14737077-Leukemia, Myeloid,
pubmed-meshheading:14737077-Male,
pubmed-meshheading:14737077-Middle Aged,
pubmed-meshheading:14737077-Mutation,
pubmed-meshheading:14737077-Proto-Oncogene Proteins,
pubmed-meshheading:14737077-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:14737077-Receptors, Cell Surface,
pubmed-meshheading:14737077-fms-Like Tyrosine Kinase 3
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pubmed:year |
2004
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pubmed:articleTitle |
Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia.
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pubmed:affiliation |
Department of Internal Medicine, Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan. sly7012@adm.cgmh.org.tw
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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