TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients

Only a minority of myelodysplastic syndrome (MDS) patients respond to hypomethylating agents (HMAs), but strong predictors of response are unknown. We sequenced 40 recurrently mutated myeloid malignancy genes in tumor DNA from 213 MDS patients collected before treatment with azacitidine (AZA) or decitabine (DEC). Mutations were examined for association with response and overall survival. The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = .036) when subclones unlikely to be detected by Sanger sequencing (allele fraction

• UD
  U.S. Department of Defense
• LA
  Leukemia and Lymphoma Society
• NI
  National Institutes of Health

  Awards: R01HL082945, CA016672, P01 CA108631
• UO
  University of Texas MD Anderson Cancer Center

  Award: CA016672
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases