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Combined Loss of Tet1 and Tet2 Promotes B Cell, but Not Myeloid Malignancies, in Mice.

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Title: Combined Loss of Tet1 and Tet2 Promotes B Cell, but Not Myeloid Malignancies, in Mice.
Author(s): Zhao, Z; Chen, L; Dawlaty, MM; Pan, F; Weeks, O; Zhou, Y; Cao, Z; Shi, H; Wang, J; Lin, L; Chen, S; Yuan, W; Qin, Z; Ni, H; Nimer, SD; Yang, FC; Jaenisch, R; Yin, P; Xu, M
Subject(s): CD45 antigen CD71 antigen leukosialin Myc protein acute lymphoblastic leukemia animal cell
Abstract: TET1/2/3 are methylcytosine dioxygenases that regulate cytosine hydroxymethylation. Tet1/2 are abundantly expressed in HSC/HPCs and are implicated in hematological malignancies. Tet2 deletion in mice causes myeloid malignancies, while Tet1-null mice develop B cell lymphoma after an extended period of latency. Interestingly, TET1/2 are often concomitantly downregulated in acute B-lymphocytic leukemia. Here, we investigated the overlapping and non-redundant functions of Tet1/2 using Tet1/2 double-knockout (DKO) mice. DKO and Tet2(-/-) HSC/HPCs show overlapping and unique 5 hmC and 5 mC profiles. DKO mice exhibit strikingly decreased incidence and delayed onset of myeloid malignancies in comparison to Tet2(-/-) mice and in contrast develop lethal B cell malignancies. Transcriptome analysis of DKO tumors reveals expression changes in many genes dysregulated in human B cell malignancies, including LMO2, BCL6, and MYC. These results highlight the critical roles of TET1/2 individually and together in the pathogenesis of hematological malignancies.
Issue Date: 2015-11-24
Publisher: Elsevier (Cell Press)
Citation Info: Zhao, Z., Chen, L., Dawlaty, M. M., Pan, F., Weeks, O., Zhou, Y., Cao, Z., Shi, H., Wang, J., Lin, L., Chen, S., Yuan, W., Qin, Z., Ni, H., Nimer, S. D., Yang, F. C., Jaenisch, R., Jin, P. and Xu, M. Combined Loss of Tet1 and Tet2 Promotes B Cell, but Not Myeloid Malignancies, in Mice. Cell Reports. 2015. 13(8): 1692-1704. DOI: 10.1016/j.celrep.2015.10.037.
Type: Article
Description: This is a copy of an article published in Elsevier (Cell Press). © Zhao et al., 2015, Cell Reports 13, 1692–1704 November 24, 2015. © 2015 The Authors. http://dx.doi.org/10.1016/j.celrep.2015.10.037
URI: http://hdl.handle.net/10027/20759
ISSN: 2211-1247
Sponsor: This work was supported by grants from the NIH (HL112294 to M.X., CA172408 to M.X. and F.-C.Y., NS079625 and MH102690 to P.J., HDO45022 and CA084198 to R.J.), Simons Foundation (to R.J. and P.J.), and National Nature Science Foundation of China (#81328003 to W.Y.).
Date Available in INDIGO: 2016-06-13
 

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