MYELOID NEOPLASIA TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients

P 5 .036) when subclones unlikely to be detected by Sanger sequencing (allele fraction < 10%) were treated as wild-type (WT). Response rates were highest in the subset of TET2 mutant patients without clonal ASXL1 mutations (OR 3.65, P 5 .009). Mutations of TP53 (hazard ratio [HR] 2.01, P 5 .002) and PTPN11 (HR 3.26, P 5 .006) were associated with shorter overall survival but not drug response. Murine-competitive bone marrowtransplantationfollowedbytreatmentwithAZAdemonstratedthat Tet2 -nullcells have an engraftment advantage over Tet2 -WT cells. AZA significantly decreased this advantagefor Tet2 -null cells ( P 5 .002) but not Tet2 -WT cells ( P 5 .212). Overall, Tet2 loss appears to sensitize cells to treatment with AZA in vivo, and TET2 mutations can identify patients more likely to respond to HMAs. ( Blood . 2014;124(17):2705-2712)

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