Source:http://linkedlifedata.com/resource/pubmed/id/19109228
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
2009-4-24
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pubmed:abstractText |
Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1 mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P = .01) and not reached versus 32 months (P = .004) in patients with NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent good prognostic factor for EFS and OS (P = .02 and P = .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/F-Box Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBXW7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:AsnafiVahidV,
pubmed-author:BénéMarie-ChristineMC,
pubmed-author:BaleydierFrédéricF,
pubmed-author:BeldjordKheiraK,
pubmed-author:BuzynAgnèsA,
pubmed-author:DombretHervéH,
pubmed-author:FagotThierryT,
pubmed-author:FrancisDanielD,
pubmed-author:HuguetFrançoiseF,
pubmed-author:IfrahNorbertN,
pubmed-author:Le NoirSandrineS,
pubmed-author:LeguayThibautT,
pubmed-author:MacintyreElizabethE,
pubmed-author:RemanOumedalyO,
pubmed-author:SimonArnauldA,
pubmed-author:TavernierEmmanuelleE,
pubmed-author:ThomasXavierX,
pubmed-author:TurlurePascalP,
pubmed-author:VernantJean-PaulJP,
pubmed-author:WitzFrancisF
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
113
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3918-24
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pubmed:dateRevised |
2011-5-23
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pubmed:meshHeading |
pubmed-meshheading:19109228-Adult,
pubmed-meshheading:19109228-Cell Cycle Proteins,
pubmed-meshheading:19109228-F-Box Proteins,
pubmed-meshheading:19109228-Genotype,
pubmed-meshheading:19109228-Humans,
pubmed-meshheading:19109228-Mutation,
pubmed-meshheading:19109228-Phenotype,
pubmed-meshheading:19109228-Precursor T-Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:19109228-Prognosis,
pubmed-meshheading:19109228-Receptor, Notch1,
pubmed-meshheading:19109228-Societies, Medical,
pubmed-meshheading:19109228-Survival Rate,
pubmed-meshheading:19109228-Time Factors,
pubmed-meshheading:19109228-Treatment Outcome,
pubmed-meshheading:19109228-Ubiquitin-Protein Ligases
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pubmed:year |
2009
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pubmed:articleTitle |
NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study.
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pubmed:affiliation |
Université Paris 5 Descartes and Assistance Publique Hôpitaux de Paris (AP-HP) and Hematology Department, Hôpital Necker-Enfants-Malades, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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