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UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8

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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.

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Acknowledgements

We thank technical help and valuable advice from all the laboratory members and FACS Core Laboratory at the Institute of Medical Science, the University of Tokyo. This work was supported in part by Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant numbers JP16K09841, JP20K08706 to TF) and Grant from Children’s Cancer Association of Japan (to TF).

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Authors and Affiliations

  1. Department of Cellular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Tomofusa Fukuyama & Toshio Kitamura

  2. Research Institute for Clinical Oncology, Saitama Cancer Center, 780 Ina, Saitama, 362-0806, Japan

    Tomofusa Fukuyama & Tomoko Kozu

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  1. Tomofusa Fukuyama
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  2. Toshio Kitamura
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Correspondence to Tomofusa Fukuyama.

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Fukuyama, T., Kitamura, T. & Kozu, T. UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8. Int J Hematol 115, 686–693 (2022). https://doi.org/10.1007/s12185-022-03303-1

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