The catalytic activity of tet2 is essential for its myeloid malignancy-suppressive function in hematopoietic stem/progenitor cells

Access through your institution Buy or subscribe 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 This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

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Contact customer support REFERENCES * Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A _et al_. Mutation in TET2 in myeloid cancers. _N Engl J Med_ 2009; 360: 2289–2301.

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1179–1181. Article  CAS  Google Scholar  Download references 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. AUTHOR INFORMATION Author notes * Z Zhao and S Chen: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * 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 * 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 *

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 * Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA H Ni Authors * Z Zhao View author publications You can also search for this author

inPubMed Google Scholar * S Chen View author publications You can also search for this author inPubMed Google Scholar * X Zhu View author publications You can also search for this author

inPubMed Google Scholar * F Pan View author publications You can also search for this author inPubMed Google Scholar * R Li View author publications You can also search for this author

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inPubMed Google Scholar * H Ni View author publications You can also search for this author inPubMed Google Scholar * F-C Yang View author publications You can also search for this author

inPubMed Google Scholar * M Xu View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to F-C Yang or M Xu. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies this paper on the _Leukemia_ website SUPPLEMENTARY

INFORMATION SUPPLEMENTARY INFORMATION (DOC 119 KB) SUPPLEMENTARY FIGURES (PDF 1603 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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).

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