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    LSK derived LSK- cells have a high apoptotic rate related to survival regulation of hematopoietic and leukemic stem cells

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    Authors
    Peng, Cong
    Chen, Yaoyu
    Shan, Yi
    Zhang, Haojian
    Guo, Zhiru
    Li, Dongguang
    Li, Shaoguang
    UMass Chan Affiliations
    Department of Medicine, Division of Hematology/Oncology
    Document Type
    Journal Article
    Publication Date
    2012-06-04
    Keywords
    Bone Marrow Cells
    Hematopoietic Stem Cells
    Cancer Biology
    Cell and Developmental Biology
    Hematology
    Life Sciences
    Medicine and Health Sciences
    
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    Abstract
    A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell population derived from HSC-containing Lin(-)Sca-1(+)c-Kit(+) (LSK) cells has significantly higher numbers of apoptotic cells. Depletion of LSK cells by radiation or the cytotoxic chemical 5-fluorouracil results in an expansion of the LSK(-) population. In contrast, the LSK(-) population is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting Alox5 or by inhibiting heat shock protein 90 causes an increase in this LSK(-) population. The transition of LSK to LSK(-) cells is controlled by the Icsbp gene and its downstream gene Lyn, and regulation of this cellular transition is critical for the survival of normal LSK cells and LSCs. These results indicate a potential function of the LSK(-) cells in the regulation of LSK cells and LSCs.
    Source
    Peng C, Chen Y, Shan Y, Zhang H, Guo Z, et al. (2012) LSK Derived LSK– Cells Have a High Apoptotic Rate Related to Survival Regulation of Hematopoietic and Leukemic Stem Cells. PLoS ONE 7(6): e38614. doi:10.1371/journal.pone.0038614. Link to article on publisher's site
    DOI
    10.1371/journal.pone.0038614
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/39542
    PubMed ID
    22675576
    Related Resources
    Link to Article in PubMed
    Rights
    Copyright: © 2012 Peng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0038614
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