Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome.
Blood
; 114(12): 2386-92, 2009 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-19602710
ABSTRACT
To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD-positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITD-mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD-positive AML. The clinical trials described herein have been registered as follows AML HD93 (already published in 2003), AML HD98A (NCT00146120; http//www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242; http//www.ClinicalTrials.gov).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Resistencia a Medicamentos Antineoplásicos
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Duplicação Gênica
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Sequências de Repetição em Tandem
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Tirosina Quinase 3 Semelhante a fms
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Mutação
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Guideline
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Blood
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha