Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms.
作者： F Traina , V Visconte , P Elson , A Tabarroki , A M Jankowska
DOI: 10.1038/LEU.2013.269
关键词:
摘要: 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 92 MDS related disorders who received 5-azacytidine (n=55), decitabine (n=26) or both (n=11). status correlated overall rate (ORR), progression-free survival (PFS) (OS) by univariate multivariate analysis. Risk stratification models were created. TET2, DNMT3A, IDH1/IDH2, ASXL1, CBL, RAS SF3B1 found 18, 9, 8, 26, 3, 2 13% of patients, respectively. In analysis, TET2(MUT) and/or DNMT3A(MUT) (P=0.03), platelets > = 100 × 10(9)/l (P=0.007) WBC 10 g/dl (P=0.01). Better OS associated ASXL1(WT) (P=0.008) SF3B1(MUT) (P=0.01), and, similar PFS, cytogenetic risk (P=0.0002), age (P=0.02) hemoglobin (P=0.04). These data support the role as predictive treated DNMT inhibitors.
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