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Type: Artigo de periódico
Title: Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms
Author: Traina, F
Visconte, V
Elson, P
Tabarroki, A
Jankowska, AM
Hasrouni, E
Sugimoto, Y
Szpurka, H
Makishima, H
O'Keefe, CL
Sekeres, MA
Advani, AS
Kalaycio, M
Copelan, EA
Saunthararajah, Y
Saad, STO
Maciejewski, JP
Tiu, RV
Abstract: We hypothesized that specific molecular mutations are important biomarkers for response to DNA methyltransferase inhibitors (DNMT inhibitors) and may have prognostic value in patients with myelodysplastic syndromes (MDS). Mutational analysis was performed in 92 patients with MDS and related disorders who received 5-azacytidine (n = 55), decitabine (n = 26) or both (n = 11). Mutational status was correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Risk stratification models were created. TET2, DNMT3A, IDH1/IDH2, ASXL1, CBL, RAS and SF3B1 mutations were found in 18, 9, 8, 26, 3, 2 and 13% of patients, respectively. In multivariate analysis, TET2(MUT) and/or DNMT3A(MUT) (P = 0.03), platelets >= 100 x 10(9)/l (P = 0.007) and WBC < 3.0 x 10(9)/l (P = 0.03) were independent predictors of better response. TET2(MUT) and/or DNMT3A(MUT) (P = 0.04) status was also independently prognostic for improved PFS, as were good or intermediate cytogenetic risk (P<0.0001), age<60 (P = 0.0001), treatment with both 5-azacytidine and decitabine (P = 0.02) and hemoglobin >= 10 g/dl (P = 0.01). Better OS was associated with ASXL1(WT) (P = 0.008) and SF3B1(MUT) (P = 0.01), and, similar to PFS, cytogenetic risk (P = 0.0002), age (P = 0.02) and hemoglobin (P = 0.04). These data support the role of molecular mutations as predictive biomarkers for response and survival in MDS patients treated with DNMT inhibitors.
Subject: DNMT inhibitors
molecular mutations
prognostic factors
Country: Inglaterra
Editor: Nature Publishing Group
Rights: fechado
Identifier DOI: 10.1038/leu.2013.269
Date Issue: 2014
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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