Ring1A and Ring1B inhibit expression of Glis2 to maintain murine AML stem cells.

Eradication of chemotherapy-resistant leukemia stem cells is expected to improve treatment outcomes in patients with acute myelogenous leukemia (AML). In a mouse model of AML expressing the fusion, we found that Ring1A and Ring1B, components of Polycomb repressive complex 1, play crucial roles in maintaining AML stem cells. Deletion of and (/) from AML cells diminished self-renewal capacity and induced the expression of numerous genes, including Overexpression of caused AML cells to differentiate into mature cells, whereas knockdown in /-deficient cells inhibited differentiation. Thus, Ring1A/B regulate and maintain AML stem cells in part by repressing expression, which promotes their differentiation. These findings provide new insights into the mechanism of AML stem cell homeostasis and reveal novel targets for cancer stem cell therapy.