Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients.
Haematologica
; 95(5): 745-51, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20133893
ABSTRACT
BACKGROUND:
Internal tandem duplications of the FLT3 gene (FLT3-ITDs) are frequent in patients with acute promyelocytic leukemia (APL), however its clinical impact remains controversial. DESIGN ANDMETHODS:
We analyzed the prognostic significance of FLT3-ITD mutant level and size, as well as FLT3-D835 point mutations, PML-RARalpha expression and other predictive factors in 129 APL patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86) PETHEMA trials.RESULTS:
FLT3-ITDs and D835 mutations were detected in 21% and 9% of patients, respectively. Patients with increased ITD mutant/wild-type ratio or longer ITD size displayed shorter 5-year relapse-free survival (RFS) (P=0.048 and P<0.0001, respectively). However, patients with D835 mutations did not show differences in RFS or overall survival (OS). Moreover, patients with initial normalized copy number (NCN) of PML-RARalpha transcripts less than the 25(th) percentile had adverse clinical features and shorter 5-year RFS (P<0.0001) and OS (P=0.004) compared to patients with higher NCN. Patients with low NCN showed increased incidence of ITDs (P=0.001), with higher ratios (P<0.0001) and/or longer sizes (P=0.007). Multivariate analysis showed that long FLT3-ITD (P=0.001), low PML-RARalpha levels (P=0.004) and elevated WBC counts (>10x10(9)/L) (P=0.018) were independent predictors for shorter RFS. We identified a subgroup of patients with high WBC, long FLT3-ITD and low NCN of transcripts that showed an extremely bad prognosis (5-year RFS 23.4%, P<0.0001).CONCLUSIONS:
In conclusion, FLT3-ITD size and PML-RARalpha transcript levels at diagnosis could contribute to improve the risk stratification in APL.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Promielocítica Aguda
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Regulação Neoplásica da Expressão Gênica
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Proteínas de Fusão Oncogênica
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Sequências de Repetição em Tandem
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Tirosina Quinase 3 Semelhante a fms
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Espanha