Uncovering a unique role for DNA methylation in hematopoietic and leukemic stem cells

IL-1β inhibits self-renewal capacity of dormant CD34+/CD38−acute myelogenous leukemia cellsin vitroandin vivo

“…These observations clearly indicate that the expression of IL‐1β was downregulated by epigenetic mechanisms in dormant leukemia cells. Previous studies showed that DNA methylation was critical for the capacity of LSCs to exert self‐renewal and multilineage fate programs . In addition, DNA methyltransferase 1 ( Dnmt1 ), but not Dnmt3a or Dnmt3b , was highly expressed in MLL‐AF9‐induced LSCs, and haploinsufficiency of DNMT1 impaired the self‐renewal capacity of MLL‐AF9‐induced LSCs .…”

“…Previous studies showed that DNA methylation was critical for the capacity of LSCs to exert self-renewal and multilineage fate programs. 30 In addition, DNA methyltransferase 1 (Dnmt1), but not Dnmt3a or Dnmt3b, was highly expressed in MLL-AF9induced LSCs, 31 and haploinsufficiency of DNMT1 impaired the self-renewal capacity of MLL-AF9-induced LSCs. 31 Teneleven translocation 2 (TET2), which converts 5-methylcytosine to 5-hydroxymethylcytosine and plays an important role in the regulation of DNA methylation, was mutated with high frequencies in multiple forms of myeloid malignancies including AML.…”