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Blood, 15 January 2007, Vol. 109, No. 2, pp. 756-762. Prepublished online as a Blood First Edition Paper on August 31, 2006; DOI 10.1182/blood-2006-01-011007. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-01-011007v1 109/2/756    most recent Alert me when this article is cited Alert me if a correction is posted 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 Yao, Y.-G. Articles by Young, N. S Search for Related Content PubMed PubMed Citation Articles by Yao, Y.-G. Articles by Young, N. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 19, 2006 Accepted August 18, 2006 Mitochondrial DNA sequence variation in single cells from leukemia patients Yong-Gang Yao*, Yoji Ogasawara, Sachiko Kajigaya, Jeffrey J Molldrem, Roberto P Falcao, Maria-Carolina Pintao, J P McCoy, Jr, Edgar G Rizzatti, and Neal S Young NHLBI, NIH, Bethesda, MD, USA University of Texas M.D. Anderson Cancer Center, Houston, TX, USA University of Sao Paulo at Ribeirao Preto Medical School, Ribeirao Preto, Brazil * Corresponding author; email: ygyaozh{at}yahoo.com. A high frequency of mtDNA somatic mutation has been observed in many tumors as well as in aging tissues. In this study, we analyzed mtDNA control region sequence variation in 3534 single normal cells and individual blasts from 18 leukemia patients and 10 healthy donors, to address the mutation process in leukemic cells. We found significant differences in mtDNA sequence, as represented by the number of haplotypes and the mean number of cells with each nonaggregate haplotype in a population of cells, in patients compared to controls. Patients with similar clinical leukemia types, particularly AML, did not show a uniform pattern of sequence variation in single blasts. Some relapsed patients presented a complex shift of major haplotypes in single cells. Four patients showed high frequencies of cells containing mutations 189, 260, 16150, and 16488, respectively, as a result of clonal expansion, and could be considered as potential markers for their respective disease progression. To our knowledge, this is the first large-scale study of mtDNA variation in single malignant cells. Our results suggest that the somatic mutation process in leukemia is complex, leading to diverse levels of genetic alterations due to either intrinsic aspects of leukemia pathophysiology and/or chemotherapy effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-G. Yao, F. M. Ellison, J. P. McCoy, J. Chen, and N. S. Young Age-dependent accumulation of mtDNA mutations in murine hematopoietic stem cells is modulated by the nuclear genetic background Hum. Mol. Genet., February 1, 2007; 16(3): 286 - 294. [Abstract] [Full Text] [PDF]

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