Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia

Figure 3

Effect of DNMT3A mutations on protein function and expression. (a) CpG islands methylation analysis. The bars represent mean ± standard deviation (SD) of the absolute 5-mC level (percentage of 5-mC left axis; SD values are barely detectable due to low values). Dots represent the DNMT3A VAF in the analyzed samples (right axis). A BM sample from an AML patient harbouring the DNMT3A R882H mutation (VAF 37.0%) was used for comparison (wt: wildtype; R882H: canonical mutation; Dx: diagnosis; F-UP: follow-up; R: relapse). (b) Western blot analyses of DNMT3A expression in representative AML cases with wt-DNMT3A and R882H mutation, followed by diagnosis and follow-up of AML#1, diagnosis and relapse of AML#2 (wt: wildtype; Dx: diagnosis; F-UP: follow-up; R: relapse). β-actin was used for loading normalization and quantification. Numbers represent DNMT3A levels normalized on the wt sample.

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