UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8

Int J Hematol. 2022 May;115(5):686-693. doi: 10.1007/s12185-022-03303-1. Epub 2022 Feb 12.

Abstract

The chimeric oncogene AML1-MTG8 (RUNX1-RUNX1T1) is generated in t(8;21) acute myeloid leukemia (AML). Here, we report a novel interaction of MTG8/RUNX1T1/ETO with UBC9/UBE2I. AML1-MTG8 protein also interacted with UBC9, suggesting a role in leukemogenesis. Overexpression of UBC9 in Kasumi-1 attenuated myeloid differentiation induced by all-trans retinoic acid, G-CSF, and GM-CSF (AGGM), which was judged by suppression of CD11b. In addition, the UBC9 inhibitor 2-D08 accelerated myeloid differentiation induced by AGGM in two t(8;21) AML cell lines, Kasumi-1 and SKNO-1. These data suggest that UBC9 may play a role in leukemogenesis in t(8;21) AML by working with AML1-MTG8 to suppress myeloid differentiation. Therefore, UBC9 may be a good target for new differentiation therapy against t(8;21) AML.

Keywords: AML1; ETO; MTG8; RUNX1; UBC9.

MeSH terms

  • Cell Differentiation
  • Cell Line
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Oncogene Proteins, Fusion* / genetics
  • Oncogene Proteins, Fusion* / metabolism
  • RUNX1 Translocation Partner 1 Protein / genetics
  • Translocation, Genetic

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein