TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics

Author:

Chou Wen-Chien12,Chou Sheng-Chieh2,Liu Chieh-Yu3,Chen Chien-Yuan2,Hou Hsin-An2,Kuo Yuan-Yeh4,Lee Ming-Cheng2,Ko Bor-Sheng2,Tang Jih-Luh2,Yao Ming2,Tsay Woei2,Wu Shang-Ju2,Huang Shang-Yi2,Hsu Szu-Chun1,Chen Yao-Chang1,Chang Yi-Chang1,Kuo Yi-Yi1,Kuo Kuan-Ting5,Lee Fen-Yu5,Liu Ming-Chi5,Liu Chia-Wen5,Tseng Mei-Hsuan2,Huang Chi-Fei2,Tien Hwei-Fang2

Affiliation:

1. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan;

2. Department of Internal Medicine Division of Hematology, National Taiwan University Hospital, Taipei, Taiwan;

3. Biostatistics Consulting Laboratory, Department of Nursing, National Taipei College of Nursing, National Taiwan University Hospital, Taipei, Taiwan;

4. Graduate Institute of Oncology, National Taiwan University Hospital, Taipei, Taiwan; and

5. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

Abstract

Abstract The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1+/FLT3-ITD− or CEBPA+). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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