Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia

Hematopoietic stem cells (HSCs) maintain homeostasis in the hematopoietic ecosystem, which is tightly regulated at multiple layers. Acute myeloid leukemia (AML) is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells (LSCs). Since somatic mutations in DNA methylation-related genes frequently occur in AML, DNA methylation is widely altered and functions as a starting engine for initiating AML. Additionally, RNA modifications, especially N⁶-methyladenosine (m⁶A), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of m⁶A modifications to facilitate cells with hallmarks of cancer. Given the complex pathogenesis and poor prognosis of AML, it is important to fully understand its pathogenesis. Here, we mainly focus on DNA methylation and RNA m⁶A modification in hematopoiesis and AML and summarize recent advances in this field.