https://scholars.lib.ntu.edu.tw/handle/123456789/502695
Title: | Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides prognostic information | Authors: | WEN-CHIEN CHOU HSIN-AN HOU Liu C.-Y. Chen C.-Y. LIANG-IN LIN Huang Y.-N. Chao Y.-C. Hsu C.-A. Huang C.-F. HWEI-FANG TIEN |
Issue Date: | 2011 | Journal Volume: | 22 | Journal Issue: | 3 | Start page/Pages: | 696-704 | Source: | Annals of Oncology | Abstract: | Background: The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information. Patients and methods: We measured mutant quantity in 493 serial samples from 55 patients with a median followup time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed. Results: We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ?3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032). Conclusions: Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1. ? The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502695 | ISSN: | 0923-7534 | DOI: | 10.1093/annonc/mdq402 | SDG/Keyword: | anthracycline; CD135 antigen; cytarabine; doxorubicin; idarubicin; nucleophosmin; retinoic acid; acute granulocytic leukemia; adolescent; adult; aged; article; cancer chemotherapy; cancer relapse; cancer survival; controlled study; disease free survival; drug megadose; female; gene duplication; gene mutation; genetic marker; human; internal tandem duplication; major clinical study; male; minimal residual disease; molecular dynamics; multiple cycle treatment; nucleotide sequence; outcome assessment; overall survival; priority journal; prognosis; quantitative study; sensitivity analysis; trend study; wild type; Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Disease-Free Survival; Female; fms-Like Tyrosine Kinase 3; Genetic Association Studies; Genetic Markers; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Molecular Sequence Data; Multivariate Analysis; Mutagenesis, Insertional; Neoplasm, Residual; Nuclear Proteins; Prognosis; Sequence Analysis, DNA; Young Adult |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.