Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation.
BACKGROUND
Despite current interest in the biology and diagnostic applications of cell-free DNA in plasma and serum, the cellular origin of this DNA is poorly understood. We used a sex-mismatched bone marrow transplantation model to study the relative contribution of hematopoietic and nonhematopoietic cells to circulating DNA.


METHODS
We studied 22 sex-mismatched bone marrow transplantation patients. Paired buffy coat and plasma samples were obtained from all 22 patients. Matching serum samples were also obtained from seven of them. Plasma DNA, serum DNA, and buffy coat were quantified by real-time PCR of the SRY and beta-globin gene DNA. To investigate the effects of blood drawing and other preanalytical variables on plasma DNA concentrations, blood samples were also collected from 14 individuals who had not received transplants. The effects of blood sampling by syringe and needle, centrifugation, and time delay in blood processing were studied.


RESULTS
The median percentage of Y-chromosome DNA in the plasma in female patients receiving bone marrow from male donors (59.5%) differed significantly (P <0.001) from that in the male patients receiving bone marrow from female donors (6.9%). This indicated that plasma DNA in the bone marrow transplantation recipients was predominantly of donor origin. Compared with paired plasma samples, serum samples had a median 14-fold higher DNA concentration, with the additional DNA being of donor origin. Control experiments indicated that none of the three tested preanalytical variables contributed to a significant change in cell-free DNA concentration.


CONCLUSIONS
After bone marrow transplantation, the DNA in plasma and serum is predominantly hematopoietic in origin. Apart from the biological implications of this observation, this finding suggests that plasma and serum can be used as alternative materials for the study of postbone marrow transplantation chimerism.
Lui
Yanni Y N
YY
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
Chik
Ki-Wai
KW
Chiu
Rossa W K
RW
Ho
Cheong-Yip
CY
Lam
Christopher W K
CW
Lo
Y M Dennis
YM
D016026:Bone Marrow Transplantation; D002451:Cell Compartmentation; D004247:DNA / Q000097:blood* / Q000235:genetics; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D010949:Plasma; D012737:Sex Factors; D018183:Transplantation Chimera
D004247:DNA