As seen above, one reason for SETD2 being involved in MLL leukemia may be because SETD2 deficiency induces DNA replication stress in Hematopoietic Stem Cells (HSCs) which results in proliferation and cell cycle abnormalities, genomic instability, hence leading to the accumulation of secondary mutation(s) that synergistically contributes to tumorigenesis [36,53]. The gene discussed is KMT2A; the disease is leukemia.