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

UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8

Tomofusa Fukuyama  1   2 , Toshio Kitamura  3 , Tomoko Kozu  4
Affiliations

UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8

Tomofusa Fukuyama et al. Int J Hematol. 2022 May.

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.

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