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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3783-3792. Prepublished online as a Blood First Edition Paper on August 3, 2009; DOI 10.1182/blood-2009-06-227843. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-06-227843v1 114/18/3783    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Hu, X. Articles by Cheng, T. PubMed PubMed Citation Articles by Hu, X. Articles by Cheng, T. Related Collections Hematopoiesis and Stem Cells Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model Xiaoxia Hu13, Hongmei Shen3,4, Chen Tian1, Hui Yu3, Guoguang Zheng1, Richard XuFeng3, Zhenyu Ju5, Jing Xu1, Jianmin Wang2, and Tao Cheng1,3 1 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China; 2 Department of Hematology, Changhai Hospital, Shanghai, China; 3 Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA; 4 The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Department of Surgery, University of Pittsburgh School of Medicine, PA; and 5 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China The predominant outgrowth of malignant cells over their normal counterparts in a given tissue is a shared feature for all types of cancer. However, the impact of a cancer environment on normal tissue stem and progenitor cells has not been thoroughly investigated. We began to address this important issue by studying the kinetics and functions of hematopoietic stem and progenitor cells in mice with Notch1-induced leukemia. Although hematopoiesis was progressively suppressed during leukemia development, the leukemic environment imposed distinct effects on hematopoietic stem and progenitor cells, thereby resulting in different outcomes. The normal hematopoietic stem cells in leukemic mice were kept in a more quiescent state but remained highly functional on transplantation to nonleukemic recipients. In contrast, the normal hematopoietic progenitor cells in leukemic mice demonstrated accelerated proliferation and exhaustion. Subsequent analyses on multiple cell-cycle parameters and known regulators (such as p21, p27, and p18) further support this paradigm. Therefore, our current study provides definitive evidence and plausible underlying mechanisms for hematopoietic disruption but reversible inhibition of normal hematopoietic stem cells in a leukemic environment. It may also have important implications for cancer prevention and treatment in general. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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