SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-10-3035. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3035v1 102/5/1626    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Reese, J. S. Articles by Gerson, S. L. Search for Related Content PubMed PubMed Citation Articles by Reese, J. S. Articles by Gerson, S. L. Related Collections Hematopoiesis and Stem Cells Neoplasia Apoptosis Cell Cycle Cell Adhesion and Motility Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1626-1633 HEMATOPOIESIS Repopulating defect of mismatch repair–deficient hematopoietic stem cells Jane S. Reese, Lili Liu, and Stanton L. Gerson From the Division of Hematology/Oncology and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH. Mismatch repair deficiency is associated with carcinogenesis, increased spontaneous and induced mutagenesis, and resistance to methylating agents. In humans, leukemias and lymphomas arise in the background of mismatch repair deficiency, raising the possibility that hematopoiesis is abnormal as well. To address hematopoiesis in MSH2–/– mice, we collected marrow and performed serial transplantations of these cells, alone or mixed with wild-type cells, into lethally irradiated healthy mice. Transplant recipients were observed or treated with the methylating agent, temozolomide (TMZ). Methylating agent tolerance was evident by the competitive survival advantage of MSH2–/– marrow progenitors compared with wild-type cells after each TMZ exposure. However, serial repopulation by MSH2–/– cells was deficient compared with wild-type cells. In recipients of mixed populations, the MSH 2–/– cells were lost from the marrow, and mice receiving MSH2–/– cells plus TMZ could not be reconstituted in the third passage, whereas all wild-type cell recipients survived. No differences in telomere length, cell cycle distribution, or homing were observed, but an increase in microsatellite instability was seen in the MSH2–/– early progenitor colony-forming unit (CFU) and Sca+Kit+lin–-derived clones. Thus, mismatch repair deficiency is associated with a hematopoietic repopulation defect and stem cell exhaustion because of accumulation of genomic instability. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Kenyon and S. L. Gerson The role of DNA damage repair in aging of adult stem cells Nucleic Acids Res., December 26, 2007; (2007) gkm1064v1. [Abstract] [Full Text] [PDF] S. Salati, E. Bianchi, R. Zini, E. Tenedini, D. Quaglino, R. Manfredini, and S. Ferrari Eosinophils, but not neutrophils, exhibit an efficient DNA repair machinery and high nucleolar activity Haematologica, October 1, 2007; 92(10): 1311 - 1318. [Abstract] [Full Text] [PDF] J. Offman, G. Opelz, B. Doehler, D. Cummins, O. Halil, N. R. Banner, M. M. Burke, D. Sullivan, P. Macpherson, and P. Karran Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation Blood, August 1, 2004; 104(3): 822 - 828. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020