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The catalytic activity of TET2 is essential for its myeloid malignancy-suppressive function in hematopoietic stem/progenitor cells

Leukemia volume 30, pages 1784–1788 (2016)Cite this article

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Mutations/deletions of the TET2 gene frequently occur in multiple spectra of myeloid malignancies, including myelodysplastic syndrome, myeloproliferative neoplasm (MPN), acute myeloid leukemia and chronic myelomonocytic leukemia (CMML).1, 2, 3, 4 TET2 mutations/deletions are often heterozygous and ancestral in these myeloid malignancies.1, 2, 3, 4 TET2 plays an important role in hematopoietic stem cell (HSC) biology, and Tet2 loss leads to an increased HSC self-renewal and skewed differentiation favoring granulocytic/monocytic lineage.5, 6, 7, 8 Furthermore, Tet2-deletion (Tet2−/−) or -haploinsufficiency (Tet2+/−) leads to myeloid malignancies in mice.5, 6, 7 TET2, therefore, acts as a tumor suppressor in hematopoiesis.

The TET family of proteins shares the conserved Cys-rich domain and double-stranded beta helix domain, which are the catalytic center of Fe2+- and 2-oxoglutarate-dependent dioxygenases.9 TETs exhibit unique enzymatic function to facilitate the DNA demethylation process, oxidizing 5-methylcytosine to 5-hydroxymethylcytosin (5hmC), 5-formylcytosine and 5-carboxylcytosine in a stepwise manner.10, 11, 12

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Acknowledgements

This work was supported by grants from the NIH (HL112294 to MX, CA172408 and CA185751 to MX and F-CY), and National Nature Science Foundation of China (#81328003 to WY).

Author contributions

ZZ, SC, XZ and PF performed the experiments and analyzed the data; HN reviewed the blood smears and histopathologic sections; ZZ, RL,YZ and WY performed experiments involving human specimens. F-CY and MX designed and supervised the studies, wrote the manuscript and are responsible for its final draft.

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  1. Z Zhao and S Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

    Z Zhao, S Chen, X Zhu, F Pan, F-C Yang & M Xu

  2. Department of Hematology and Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Z Zhao

  3. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    R Li, Y Zhou & W Yuan

  4. Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA

    H Ni

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  1. Z Zhao
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Correspondence to F-C Yang or M Xu.

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Zhao, Z., Chen, S., Zhu, X. et al. The catalytic activity of TET2 is essential for its myeloid malignancy-suppressive function in hematopoietic stem/progenitor cells. Leukemia 30, 1784–1788 (2016). https://doi.org/10.1038/leu.2016.56

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