Abstract
BackgroundThe impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial. A meta analysis is needed in order to assess the prognostic significance of TET2 mutation in AML.MethodsFive databases including PubMed, Cochrane, EMBase, China National Knowledge Internet (CNKI) and Wanfang database were retrieved to search studies that investigated the correlation between TET2 mutations and outcomes of AML patients. Pooled hazard ratios (HRs) and odds ratios (ORs) were used to assess the effects of TET2 mutations.ResultsSixteen studies were included. TET2 mutation was an unfavorable prognostic factor for overall survival (OS: HR = 1.386; P < 0.001) and event-free survival (EFS: HR = 1.594; P = 0.002) in patients with AML. For patients under 65 years of age, TET2 mutation predicted an inferior OS (HR = 1.310, P = 0.051) and EFS (HR = 1.429, P = 0.027). For patients with intermediate-risk cytogenetics (IR-AML), mutant TET2 had a significant association with adverse OS (HR = 0.474; P < 0.001). For patients with normal cytogenetics (CN-AML), mutant TET2 also conferred adverse OS (HR = 1.425; P < 0.001) and EFS (HR = 1.450, P < 0.001). Further, among patients with CN-AML, mutant TET2 was associated with inferior OS (HR = 2.034, P < 0.001) and EFS (HR = 2.140, P < 0.001) in the ELN favorable-risk subgroup and an inferior EFS (HR = 1.487; P < 0.001) in the ELN intermediate-Isubgroup. With respect to treatment outcome, TET2 mutation predicted a significantly lower rate of complete remission (CR) in cases with ELN favorable-risk cytogenetics (OR = 0.460, P = 0.011).ConclusionsTET2 mutation had adverse impacts on survival and treatment response in AML patients and will contribute to risk-stratification, prognosis prediction and therapy guidance.
Highlights
The impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial
After a meta-analysis, we found a significantly close relationship between TET2 mutations and intermediate-risk cytogenetics with an odds ratio (OR) of 1.765(95%confidence interval (CI): 1.212–2.569; P = 0.003; I2 = 39.7%, P = 0.159), and TET2 mutations were more infrequent in favorable-risk cytogenetics(OR = 0.547, 95%CI: 0.325–0.920; P = 0.023; I2 = 11.2%, P = 0.337)
We explored the impact of mutant TET2 on overall survival (OS) in AML patients under 65 years of age, figuring out a pooled hazard ratio (HR) of 1.310 (95%CI: 0.999–1.718; P = 0.051; heterogeneity: I2 = 24.6%, P = 0.264; Fig. 2c), while the pooled HRs for event-free survival (EFS) in the same cohort were 1.724
Summary
The impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial. Tet oncogene family member 2 gene (TET2) still has a controversial prognostic impact on AML because studies researching TET2 mutations are not plenty and their conclusions are not identical. In a meta-analysis performed by Wenjian Liu, mutant TET2 was an unfavorable prognostic factor among entire AML patients and favorable and intermediate-I subgroups based on ELN guidelines [11]. Since this meta analysis only contained 8 studies, it’s necessary to perform a updated meta analysis containing more studies to further explore the influence of TET2 mutations on clinical outcome and survival in AML patients
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