We next sought to validate these findings, first by shRNA knockdown of DNMT1 and/or DNMT3B in AML cell lines either wild-type or mutant for DNMT3A. THP-1 cells, which are wild-type for DNMT3A, and OCI-AML2 cells, which harbor a homozygous R635W mutation in the MTase domain of DNMT3A, were transduced with shRNAs targeting DNMT1 and/or DNMT3B. A shRNA targeting luciferase was used as a negative control. The gene discussed is DNMT3B; the disease is acute myeloid leukemia.