TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: A cancer and leukemia group B study

Academic Article

Abstract

  • Purpose: To determine the frequency of TET2 mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene-and microRNA-expression signatures in patients with primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods: Four-hundred twenty-seven patients with CN-AML were analyzed for TET2 mutations by polymerase chain reaction and direct sequencing and for established prognostic gene mutations. Geneand microRNA-expression profiles were derived using microarrays Results: TET2 mutations, found in 23% of patients, were associated with older age (P <.001) and higher pretreatment WBC (P =.04) compared with wild-type TET2 (TET2-wt). In the European LeukemiaNet (ELN) favorable-risk group (patients with CN-AML who have mutated CEBPA and/or mutated NPM1 without FLT3 internal tandem duplication [FLT3-ITD]), TET2-mutated patients had shorter event-free survival (EFS; P <.001) because of a lower complete remission (CR) rate (P =.007), and shorter disease-free survival (DFS; P =.003), and also had shorter overall survival (P =.001) compared with TET2-wt patients. TET2 mutations were not associated with outcomes in the ELN intermediate-I-risk group (CN-AML with wild-type CEBPA and wild-type NPM1 and/or FLT3-ITD). In multivariable models, TET2 mutations were associated with shorter EFS (P =.004), lower CR rate (P = 03), and shorter DFS (P =.05) only among favorable-risk CN-AML patients. We identified a TET2 mutation-associated gene-expression signature in favorable-risk but not in intermediate-I-risk patients and found distinct mutation-associated microRNA signatures in both ELN groups. Conclusion: TET2 mutations improve the ELN molecular-risk classification in primary CN-AML because of their adverse prognostic impact in an otherwise favorable-risk patient subset. Our data suggest that these patients may be candidates for alternative therapies © 2011 by American Society of Clinical Oncology.
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    Digital Object Identifier (doi)

    Author List

  • Metzeler KH; Maharry K; Radmacher MD; Mrózek K; Margeson D; Becker H; Curfman J; Holland KB; Schwind S; Whitman SP
  • Start Page

  • 1373
  • End Page

  • 1381
  • Volume

  • 29
  • Issue

  • 10