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

Traina, F, Visconte, V, Elson, P, Tabarroki, A, Jankowska, A M, Hasrouni, E, Sugimoto, Y, Szpurka, H, Makishima, H, O'Keefe, C L, Sekeres, M A, Advani, A S, Kalaycio, M, Copelan, E A, Saunthararajah, Y, Olalla Saad, S T, Maciejewski, J P, Tiu, R V·2014·Leukemia
DOI 10.1038/leu.2013.269
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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 > or = 100 × 10(9)/l (P=0.007) and WBC or = 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.

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Research works printed but not linked: 29

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Metadata

Authors
Traina, F., Visconte, V, Elson, P., Tabarroki, A., Jankowska, A. M., Hasrouni, E., Sugimoto, Y., Szpurka, H., Makishima, H., O'Keefe, C. L., Sekeres, M. A., Advani, A. S., Kalaycio, M., Copelan, E. A., Saunthararajah, Y., Olalla Saad, S. T., Maciejewski, J. P., & Tiu, R. V.
Venue
Leukemia
Publisher
Springer Science and Business Media LLC
Published
2013-09-18
Volume
28
Issue
1
Pages
78-87
ISSN
  • 0887-6924
  • 1476-5551
DOI
10.1038/leu.2013.269
Cited by
269
References
8
Language
en
Licence

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