Table 1: Key genetic mutations thought to have implications for prognosis in AML. The genetic mutations included in the table are reviewed below. Table compiled with information from [29, 32, 35, 39, 50, 52, 58, 61, 66, 67, 73, 76, 80, 8696].

GeneMutation typeMutation frequencyConsequence of mutationPrognostic implicationsInitiating lesion

DNMT3AMainly missense
60% at R882
Often heterozygous
15–25% AMLR882 mutations reduce binding affinity and catalytic activity—LOFLikely poorer prognosis. Affected by R882/non-R882, CM, patient age Adverse prognosis in intermediate risk AMLUncertain

TET246% frame shift
Also missense, nonsense, and splice site variations
Majority heterozygous
7–23% AML
10–20% MPN/MDS
Truncated protein and consequent reduction in hydroxymethylation—LOF Poorer prognosis in favorable risk CN-AML
No effect in MPN, possibly improved prognosis in MDS
Early event, possibly initiating

IDH1 + 2Amino acid substitutions
R132 (IDH1)
R172, and R140 (IDH2)
Heterozygous
15–30% AML
5% MPN/MDS
Neomorphic gain of function
Production of 2-HG, inhibition of TET2 function
Unclear—R140Q may have favorable effect on prognosis R132H/R172K may have no effect
However some studies suggest IDH mutations have adverse impact on favorable CN-AML NPM1mut/IDHmut AML has a favorable outcome
Early event, possibly initiating

ASXL1Nonsense, missense, frame shift, and point mutations10–15% MPN/AML
10–25% MDS
Uncertain if function lost or gained—research suggests reduced ASXL1 expressionPoor prognostic marker in AML and MPNVery early, increased leukemic progression in MPN

EZH2Missense, nonsense, and frame shiftOccasional in AML
MDS 7%
MPN 3–13%
Truncated SET domain—LOF
Gain of function observed in other malignancies
Worse OS in MDS, CMML, and PMF
(del)7q poor prognostic indicator in MDS—probably in part due to loss of EZH2
Very early event in MPN, probably not leukemic initiator

LOF: loss of function.