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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms

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Autor(es):
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Traina, F. [1, 2, 3] ; Visconte, V. [1] ; Elson, P. [4] ; Tabarroki, A. [1] ; Jankowska, A. M. [1] ; Hasrouni, E. [1] ; Sugimoto, Y. [1] ; Szpurka, H. [1] ; Makishima, H. [1] ; O'Keefe, C. L. [1] ; Sekeres, M. A. [5] ; Advani, A. S. [5] ; Kalaycio, M. [5] ; Copelan, E. A. [5] ; Saunthararajah, Y. [1] ; Saad, S. T. Olalla [2] ; Maciejewski, J. P. [1, 5] ; Tiu, R. V. [1, 5]
Número total de Autores: 18
Afiliação do(s) autor(es):
[1] Cleveland Clin, Dept Translat Hematol & Oncol Res, Taussig Canc Inst, Cleveland, OH 44195 - USA
[2] Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr INCT Sangue, Campinas, SP - Brazil
[3] Univ Sao Paulo, Dept Internal Med, Sch Med, BR-14049 Ribeirao Preto, SP - Brazil
[4] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 - USA
[5] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Taussig Canc Inst, Cleveland, OH 44195 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: LEUKEMIA; v. 28, n. 1, p. 78-87, JAN 2014.
Citações Web of Science: 153
Resumo

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. (AU)

Processo FAPESP: 12/09982-8 - Investigação de alterações moleculares em neoplasias mielóides
Beneficiário:Fabíola Traina
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 11/20750-9 - 53rd ash Annual Meeting and exposition
Beneficiário:Fabíola Traina
Linha de fomento: Auxílio à Pesquisa - Reunião - Exterior