DNMT3A and acute myeloid leukemia: Treatment monitoring revealed a significant LPMD decrease at 3-5 months (-3.7%, <i>p</i> < 0.001), defining a critical window for efficacy assessment.<h4>Conclusions</h4>The LPMD algorithm reframes DNMT3A-mutant AML from a hypomethylation paradigm to a methylation disorder paradigm, revealing dual mechanisms of aberrant stabilization and maintenance failure at distinct genomic regions.