Year: 2015
Type: article
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[superscript −/−] HSC/HPCs show overlapping and unique 5hmC and 5mC profiles. DKO mice exhibit strikingly decreased incidence and delayed onset of myeloid malignancies in comparison to Tet2[superscript −/−] 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.
Authors: Zhigang Zhao, Li Chen, Meelad M. Dawlaty, Feng Pan, Ophelia Weeks, Yuan Zhou, Zeng Cao, Hui Shi, Jiapeng Wang, Li Lin, Shi Chen, Weiping Yuan, Zhaohui Qin, Hongyu Ni, Stephen D. Nimer, Feng‐Chun Yang, Rudolf Jaenisch, Peng Jin, Mingjiang Xu
Institutions: Emory University, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Florida International University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, University of Miami, Sylvester Comprehensive Cancer Center, University of Illinois Chicago
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2588081511