Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells

Haruko Shima, Emi Takamatsu-Ichihara, Mika Shino, Kazutsune Yamagata, Takuo Katsumoto, Yukiko Aikawa, Shuhei Fujita, Haruhiko Koseki, Issay Kitabayashi

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Abstract

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 MOZ-TIF2 fusion, we found that Ring1A and Ring1B, components of Polycomb repressive complex 1, play crucial roles in maintaining AML stem cells. Deletion of Ring1A and Ring1B (Ring1A/B) from MOZ-TIF2 AML cells diminished self-renewal capacity and induced the expression of numerous genes, including Glis2. Overexpression of Glis2 caused MOZ-TIF2 AML cells to differentiate into mature cells, whereas Glis2 knockdown in Ring1A/B-deficient MOZ-TIF2 cells inhibited differentiation. Thus, Ring1A/B regulate and maintain AML stem cells in part by repressing Glis2 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.

Original languageEnglish
Pages (from-to)1833-1845
Number of pages13
JournalBlood
Volume131
Issue number16
DOIs
Publication statusPublished - 2018 Apr 19

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Shima, H., Takamatsu-Ichihara, E., Shino, M., Yamagata, K., Katsumoto, T., Aikawa, Y., Fujita, S., Koseki, H., & Kitabayashi, I. (2018). Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells. Blood, 131(16), 1833-1845. https://doi.org/10.1182/blood-2017-05-787226