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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4466-4477.
Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2003-11-3949.
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Submitted November 18, 2003
Accepted February 4, 2004
Mitochondrial DNA sequence heterogeneity in circulating normal human CD34 cells and granulocytes
Myung Geun Shin, Sachiko Kajigaya, Magdalena Tarnowka, J P McCoy, Barbara C Levin, and Neal S Young*
Hematology Branch, National Heart Lung, and Blood Institute, Bethesda, MD, USA
Hematology Branch, National Heart Lung, and Blood Institute, Bethesda, MD, USA; Flow Cytometry Core Facility, National Heart Lung, and Blood Institute, Bethesda, MD, USA
Hematology Branch, National Heart Lung, and Blood Institute, Bethesda, MD, USA; Biotechnology Division, Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA
* Corresponding author; email: youngns{at}mail.nih.gov.
We have reported marked mitochondrial DNA (mtDNA) sequence heterogeneity among individual CD34 clones from adult bone marrow (BM) and the age-dependent accumulation of mtDNA mutations in this mitotically active tissue. Here we show direct evidence of clonal expansion of cells containing mtDNA mutations and that the mtDNA sequence may be easily determined using peripheral blood (PB) as a CD34 cell source. Analysis of 594 circulating CD34 clones showed that 150 (25%) had mtDNA sequences different from the same donor's corresponding aggregate sequence. Examination of single granulocytes indicated that 103 (29%) from the same six individuals showed mtDNA heterogeneity, with sequences distinct from the corresponding aggregate tissue sequence and from the sequences of other single granulocytes. Circulating and BM CD34 cells showed virtually identical patterns of mtDNA heterogeneity, and the same changes were seen in progeny granulocytes as in their progenitors, indicating that blood sampling could be utilized in studies to determine whether mtDNA reflects an individual's cumulative or recent exposure to mutagens; as a marker of individual hematopoietic progenitors, stem cells and their expansion; and for the detection of minimal residual disease in hematological malignancies of CD34 cell origin.
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