Table 1.

Frequency of gene mutations in patients with MDS or AML

GeneGene functionMutation descriptionMutation frequency in MDS (%)Mutation frequency in CN-AML (%)
DNMT3ADe novo DNA methylationRecurrent heterozygous missense mutation at R882818–25
IDH1/2Catalyzes interconversion of isocitrate and α-KGIHD1-heterozygous R132 missense IDH2-heterozygous R172 or R140 missense mutation4–116–19
TET2Oxidizes 5-mC to 5-hmC, a demethylation intermediatePrimarily biallelic mutations resulting in loss of function19–2624–27
EZH2aProgressive trimethylation of H3K27Inactivating mutations and overexpression observed in myeloid malignancies6.4Rare
ASXL1Transcription factor that maintains HOX expressionPrimarily heterozygote, monoallelic truncating mutations that deletes the PHD domain145.2
MLLH3K4 methyltransferaseTranslocations involving MLL that result in a fusion protein or partial tandem duplication mutations of MLLRare10 (de novo), 30 (secondary)
SF3B1Spliceosomal gene important for HOX gene repressionPredominantly heterozygous missense mutation at R625, H662, and K70080% in MDS-RARS and 6% in MDS without RS3–5
SRSF2Spliceosomal gene implicated in genomic stabilityHeterozygous missense mutation at P95∼2% in MDS-RARS and ∼12% in MDS w/o RS7–8
U2AF35Spliceosomal gene implicated in proper splicing of genesHeterozygous missense mutation at S34 and Q15712% (only in MDS without RS)11

Abbreviations: PHD, plant homeodomain; RS, ringed sideroblasts.

  • aEZH2 mutations are generally activating mutations in other malignancies.