Cancer Management and Research (Aug 2018)

Clinical and biological implications of IDH1/2 in acute myeloid leukemia with DNMT3Amut

  • Zhang XP,
  • Shi JL,
  • Zhang JL,
  • Yang XR,
  • Zhang GQ,
  • Yang SY,
  • Wang J,
  • Ke XY,
  • Fu L

Journal volume & issue
Vol. Volume 10
pp. 2457 – 2466

Abstract

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Xinpei Zhang,1 Jinlong Shi,2 Jilei Zhang,1 Xinrui Yang,1 Gaoqi Zhang,1 Siyuan Yang,1 Jing Wang,1 Xiaoyan Ke,1 Lin Fu1 1Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, China; 2Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China Purpose: The incidence of DNMT3A mutations in acute myeloid leukemia (AML) is quite high and often confers a poorer prognosis. Another common gene involved in AML is IDH1/2. However, the influence of IDH1/2 mutations on outcomes in DNMT3A-mutated patients remains unknown. This study aims to determine the effect of IDH1/2mut on the prognosis in patients with DNMT3A-mutated AML. Patients and methods: We screened patients from The Cancer Genome Atlas database and selected 51 patients with AML and the DNMT3A mutation, among which 16 patients (31.4%) had both DNMT3A and IDH1/2mut. Results: Among our sample, 11 cases had the IDH1 mutation (21.7%), and 5 cases had the IDH2 mutation (9.8%). Patients in the DNMT3AmutIDH1/2wild group showed a greater number of NPM1 mutation (P=0.022), and higher event-free survival (EFS) and overall survival (OS) after hematopoietic stem cell transplantation (HSCT) (P=0.010 and P=0.007, respectively). Patients in the DNMT3AmutIDH1/2mut group showed no increase in EFS or OS after HSCT or chemotherapy. Other factors, like white blood cells, bone marrow blasts, peripheral blood blasts, and mutated recurrent gene numbers had no significant influence on EFS and OS. Conclusion: The IDH1/2 gene had little influence on the prognosis of patients with the DNMT3A mutation. For patients in the DNMT3AmutIDH1/2wild group, HSCT had a more favorable therapeutic effect. For patients with DNMT3A and IDH1/2mut, chemotherapy and HSCT appeared to have similar efficacy. Keywords: acute myeloid leukemia, molecular mutations, prognosis, next-generation sequencing

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