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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 18
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: LEUKEMIA; v. 28, n. 1, p. 78-87, JAN 2014.
Web of Science Citations: 153
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. (AU)

FAPESP's process: 12/09982-8 - Investigation of molecular alterations in myeloid neoplasms.
Grantee:Fabíola Traina
Support Opportunities: Regular Research Grants
FAPESP's process: 11/20750-9 - 53rd ASH Annual Meeting and Exposition
Grantee:Fabíola Traina
Support Opportunities: Research Grants - Meeting - Abroad