Hematological malignancies are characterized by (1) a high frequency of DNA methylation regulator aberrations (e.g., those of DNMT3A, TET2, IDH1/2) and histone modifiers (e.g., those of EZH2, KMT2D/MLL2, and CREBBP), and are directly driven by epigenomic abnormalities, and (2) the epigenomic alteration-related hematopoietic stem cell-derived lineage is the cell of origin and highly permissive to epigenomic alterations. The gene discussed is KMT2D; the disease is hematologic disorder.