Your browser doesn't support javascript.
loading
TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal.
Li, Yangchan; Xue, Meilin; Deng, Xiaolan; Dong, Lei; Nguyen, Le Xuan Truong; Ren, Lili; Han, Li; Li, Chenying; Xue, Jianhuang; Zhao, Zhicong; Li, Wei; Qing, Ying; Shen, Chao; Tan, Brandon; Chen, Zhenhua; Leung, Keith; Wang, Kitty; Swaminathan, Srividya; Li, Ling; Wunderlich, Mark; Mulloy, James C; Li, Xiaobo; Chen, Hao; Zhang, Bin; Horne, David; Rosen, Steven T; Marcucci, Guido; Xu, Mingjiang; Li, Zejuan; Wei, Minjie; Tian, Jingyan; Shen, Baiyong; Su, Rui; Chen, Jianjun.
Afiliação
  • Li Y; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
  • Xue M; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Deng X; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Dong L; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Nguyen LXT; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Ren L; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Pathology, Harbin Medical University, Harbin 150081, China.
  • Han L; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110001, Liaoning, China.
  • Li C; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 31003, Zhejiang, China.
  • Xue J; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Zhao Z; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Li W; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Qing Y; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Shen C; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Tan B; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Chen Z; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Leung K; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Wang K; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Swaminathan S; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Pediatrics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
  • Li L; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Wunderlich M; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • Mulloy JC; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • Li X; Department of Pathology, Harbin Medical University, Harbin 150081, China.
  • Chen H; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Zhang B; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Horne D; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
  • Rosen ST; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; Department of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA.
  • Marcucci G; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Xu M; Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
  • Li Z; Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
  • Wei M; Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110001, Liaoning, China.
  • Tian J; State Key Laboratory of Medical Genomics, Clinical Trial Center, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: tianjypaper@163.com.
  • Shen B; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: shenby@shsmu.edu.cn.
  • Su R; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address: rsu@coh.org.
  • Chen J; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address: jianchen@coh.org.
Cell Stem Cell ; 30(8): 1072-1090.e10, 2023 08 03.
Article em En | MEDLINE | ID: mdl-37541212
ABSTRACT
TET2 is recurrently mutated in acute myeloid leukemia (AML) and its deficiency promotes leukemogenesis (driven by aggressive oncogenic mutations) and enhances leukemia stem cell (LSC) self-renewal. However, the underlying cellular/molecular mechanisms have yet to be fully understood. Here, we show that Tet2 deficiency significantly facilitates leukemogenesis in various AML models (mediated by aggressive or less aggressive mutations) through promoting homing of LSCs into bone marrow (BM) niche to increase their self-renewal/proliferation. TET2 deficiency in AML blast cells increases expression of Tetraspanin 13 (TSPAN13) and thereby activates the CXCR4/CXCL12 signaling, leading to increased homing/migration of LSCs into BM niche. Mechanistically, TET2 deficiency results in the accumulation of methyl-5-cytosine (m5C) modification in TSPAN13 mRNA; YBX1 specifically recognizes the m5C modification and increases the stability and expression of TSPAN13 transcripts. Collectively, our studies reveal the functional importance of TET2 in leukemogenesis, leukemic blast cell migration/homing, and LSC self-renewal as an mRNA m5C demethylase.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Dioxigenases Limite: Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Dioxigenases Limite: Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China