TET2 mutations in secondary acute myeloid leukemias: a French retrospective study

Abstract

Ten-eleven translocation 2 (TET2) mutations have been involved in myeloid malignancies. This retrospective study aims at evaluating the frequency and impact of TET2 mutations in 247 secondary acute myeloid leukemia cases referred to as myelodysplasia-related changes (n=201) or therapy-related (n=46) leukemias. Mutation of at least one copy of the TET2 gene was detected in 49 of 247 (19.8%) patients who presented with older age, higher hemoglobin level, higher neutrophil and monocyte counts, and lower platelet count. TET2 mutations were significantly less frequent in therapy-related (8.7%) than myelodysplasia-related changes (22.3%; P=0.035) leukemias and strongly associated with normal karyotype (P<0.001). TET2 mutations did not significantly associate with NPM1, FLT3-ITD or FLT3-D835, WT1, or N- or K-RAS mutations. Complete remission was achieved in 57% of evaluable patients who had received intensive chemotherapy. In this group, TET2 mutations did not influence the complete remission rate or overall survival.

Figures

Figure 1.

Overall survival. (A) and (B) impact of TET2 mutation in MRC-AML or TR-AML (A) and MRC-AML (B). (C) Impact of normal karyotype. (D) Impact of TET2 in AML with normal karyotype. (E) Impact of monosomal karyotype. (F) Impact of TET2 on non-monosomal karyotype AML. MUT: mutated TET2; WT: wild-type TET2; NK: normal karyotype; ANK: abnormal karyotype; MK: monosomal karyotype; NMK: non-monosomal karyotype. Log rank test for P value.