DNMT3A and acute myeloid leukemia: Furthermore, recent studies have suggested that the R882H mutation may affect the relative enzymatic preference of DNMT3A toward different CpG-flanking sequences: in comparison with wild-type DNMT3A, the R882H mutant shows stronger preference for the CG(G/A) motif over the CG(T/C) motif as substrate25, which correlates with the aberrant DNA methylation and gene expression in AML, suggesting an off-targeting effect of the DNMT3A R882H mutation that may contribute to AML pathogenesis21.