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Journal of Molecular Medicine

, Volume 96, Issue 11, pp 1267–1277 | Cite as

TRIB2 regulates the differentiation of MLLTET1 transduced myeloid progenitor cells

  • Hyeng-Soo Kim
  • Seung Hwan Oh
  • Ju-Heon Kim
  • Wern-Joo Sohn
  • Jae-Young Kim
  • Do-Hyung Kim
  • Sang-Un Choi
  • Kwon Moo Park
  • Zae Young Ryoo
  • Tae Sung Park
  • Sanggyu LeeEmail author
Original Article

Abstract

The function and mechanism of action of MLL–TET1 (MT1) fusion protein in hematological cells are unclear and require further investigation. In the present study, we found that the MT1 fusion protein attenuated the expression of Cebpa, Csf1r, and Cd11b and inhibited the differentiation of myeloid progenitor cells. Increased binding of the MT1 fusion protein to the Trib2 promoter upregulated Trib2 mRNA and protein expression and downregulated Cebpa expression. Trib2 knockdown relieved the inhibition of myeloid cell differentiation induced by the MT1 fusion protein. Thus, TRIB2 is important for the survival of leukemia cells during MT1-related leukemogenesis and is important in maintaining differentiation blockade of leukemic cells.

Key messages

• MLL–TET1 fusion decreases the 5-hmC levels in the myeloid progenitor cells.

• MLL–TET1 fusion inhibits myeloid differentiation through decreased expression of Cebpa.

• MLL–TET1 fusion blocks the differentiation of the myeloid progenitor cells by overexpressing Trib2.

• Knockdown of Trib2 in MLL–TET1 transduced cells induces myeloid differentiation.

Keywords

Leukemia MLL–TET1 MLL TET1 Trib2 

Notes

Acknowledgements

This work has supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (Grant No. NRF-2016R1C1B1010734 and NRF-2018R1D1A1B07049274).

Compliance with ethical standards

All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee of Kyungpook National University.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Supplementary material

109_2018_1700_MOESM1_ESM.pdf (535 kb)
ESM 1 (PDF 535 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hyeng-Soo Kim
    • 1
    • 2
  • Seung Hwan Oh
    • 3
  • Ju-Heon Kim
    • 1
  • Wern-Joo Sohn
    • 4
  • Jae-Young Kim
    • 4
  • Do-Hyung Kim
    • 5
  • Sang-Un Choi
    • 6
  • Kwon Moo Park
    • 7
  • Zae Young Ryoo
    • 1
  • Tae Sung Park
    • 8
  • Sanggyu Lee
    • 1
    Email author
  1. 1.School of Life Science, BK21 plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguRepublic of Korea
  2. 2.Institute of Life Science and BiotechnologyKyungpook National UniversityDaeguRepublic of Korea
  3. 3.Department of Laboratory Medicine, College of MedicineInje UniversityBusanRepublic of Korea
  4. 4.Department of Biochemistry, School of Dentistry, IHBRKyungpook National UniversityDaeguRepublic of Korea
  5. 5.Department of PhysicsKyungpook National UniversityDaeguRepublic of Korea
  6. 6.Korea Research Institute of Chemical TechnologyDaejeonRepublic of Korea
  7. 7.Department of AnatomyKyungpook National University School of MedicineDaeguRepublic of Korea
  8. 8.Department of Laboratory MedicineKyung Hee University School of MedicineSeoulRepublic of Korea

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