Mutations in recurrently mutated epigenetic modifiers in adults with AML and their clinical relevance and associations
| Gene . | Mutation effect on gene . | Mutational frequency in AML, % . | Clinical associations . | |
|---|---|---|---|---|
| 16-60 y . | >60 y . | |||
| ASXL16,19,46,47,65 | Affected by loss-of-function mutations and copy-number loss | 3-6.8 | 16.2-25 | Mutations repeatedly identified as enriched in elderly AML patients, AML with an antecedent MDS, and AML patients with RUNX1 mutations. Associated with adverse OS in patients 16-60 y and >60 y of age. In some studies, the adverse effect is only in the subset of CN-AML or intermediate-risk AML. |
| DNMT3A7,14,16,19,66 | Appear to be affected by loss-of-function mutations, effect of the recurrent Arg882 mutation not clear | 17.8-23 | 16-22 | DNMT3A mutations confer adverse risk to intermediate-risk AML patients in multiple series. In most series, this adverse risk is restricted to those patients with FLT3-ITD mutant intermediate-risk AML patients. DNMT3A-mutant patients appear to have improved outcome with high-dose induction daunorubicin therapy (90 mg/m2) as opposed to conventional dose (45 mg/m2). |
| IDH1/219,22,35,36,67-71 | Gain of function | IDH1: 7-10.9 | IDH1: 9.6-14 | Multiple conflicting reports on the prognostic impact of IDH1/2 mutations in AML. IDH1/2 mutations consistently reported to be significantly associated with NPM1 mutations and identified favorable effect of IDH2R140Q mutations on OS and especially favorable outcome of patients with both IDH1 or mutually exclusive with TET2 mutations. Studies with uniform treatments IDH2 and NPM1 mutations. |
| IDH2: 8-12.1 | IDH2: 8-19 | |||
| TET24,19,21,24,72 | Affected by loss-of-function mutations and copy-number loss | 7-10 | 19-24.5 | Repeatedly associated with adverse OS in the subset of patients with intermediate-risk AML. In several studies, prognostic effect of TET2 mutations is independent of FLT3-ITD in intermediate-risk AML. |
| Gene . | Mutation effect on gene . | Mutational frequency in AML, % . | Clinical associations . | |
|---|---|---|---|---|
| 16-60 y . | >60 y . | |||
| ASXL16,19,46,47,65 | Affected by loss-of-function mutations and copy-number loss | 3-6.8 | 16.2-25 | Mutations repeatedly identified as enriched in elderly AML patients, AML with an antecedent MDS, and AML patients with RUNX1 mutations. Associated with adverse OS in patients 16-60 y and >60 y of age. In some studies, the adverse effect is only in the subset of CN-AML or intermediate-risk AML. |
| DNMT3A7,14,16,19,66 | Appear to be affected by loss-of-function mutations, effect of the recurrent Arg882 mutation not clear | 17.8-23 | 16-22 | DNMT3A mutations confer adverse risk to intermediate-risk AML patients in multiple series. In most series, this adverse risk is restricted to those patients with FLT3-ITD mutant intermediate-risk AML patients. DNMT3A-mutant patients appear to have improved outcome with high-dose induction daunorubicin therapy (90 mg/m2) as opposed to conventional dose (45 mg/m2). |
| IDH1/219,22,35,36,67-71 | Gain of function | IDH1: 7-10.9 | IDH1: 9.6-14 | Multiple conflicting reports on the prognostic impact of IDH1/2 mutations in AML. IDH1/2 mutations consistently reported to be significantly associated with NPM1 mutations and identified favorable effect of IDH2R140Q mutations on OS and especially favorable outcome of patients with both IDH1 or mutually exclusive with TET2 mutations. Studies with uniform treatments IDH2 and NPM1 mutations. |
| IDH2: 8-12.1 | IDH2: 8-19 | |||
| TET24,19,21,24,72 | Affected by loss-of-function mutations and copy-number loss | 7-10 | 19-24.5 | Repeatedly associated with adverse OS in the subset of patients with intermediate-risk AML. In several studies, prognostic effect of TET2 mutations is independent of FLT3-ITD in intermediate-risk AML. |
CN-AML, cytogenetically normal AML; IDH, isocitrate dehydrogenase; MDS, myelodysplastic syndrome; OS, overall survival.