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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3186-3193. Prepublished online as a Blood First Edition Paper on July 18, 2008; DOI 10.1182/blood-2008-03-143925. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2008-03-143925v1 112/8/3186    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 Swierczek, S. I. Articles by Prchal, J. T. Search for Related Content PubMed PubMed Citation Articles by Swierczek, S. I. Articles by Prchal, J. T. Related Collections Hematopoiesis and Stem Cells Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Hematopoiesis is not clonal in healthy elderly women Sabina I. Swierczek1,*, Neeraj Agarwal1,*, Roberto H. Nussenzveig2,*, Gerald Rothstein3, Andrew Wilson2, Andrew Artz4, and Josef T. Prchal1,2,5 1 Division of Hematology, School of Medicine, University of Utah, Salt Lake City; 2 ARUP Laboratories, Salt Lake City, UT; 3 Division of Geriatrics, School of Medicine, University of Utah, Salt Lake City; 4 Section of Hematology-Oncology, University of Chicago, IL; and 5 Veterans Affairs Medical Center, Salt Lake City, UT Clonality assays, based on X-chromosome inactivation, discriminate active from inactive alleles. Skewing of X-chromosome allelic usage, based on preferential methylation of one of the HUMARA alleles, was reported as evidence of clonal hematopoiesis in approximately 30% of elderly women. Using a quantitative, transcriptionally based clonality assay, we reported X-chromosome–transcribed allelic ratio in blood cells of healthy women consistent with random X-inactivation of 8 embryonic hematopoietic stem cells. Furthermore, we did not detect clonal hematopoiesis in more than 200 healthy nonelderly women. In view of the susceptibility of aging hematopoietic stem cells to epigenetic dysregulation, we reinvestigated the issue of clonality in elderly women. Forty healthy women (ages 65-92 years; mean, 81.3 years) were tested by a novel, quantitative polymerase chain reaction (qPCR) transcriptional clonality assay. We did not detect clonal hematopoiesis in any of the tested subjects. We also tested DNA from the same granulocyte samples using the methylation-based HUMARA assay, and confirmed previous reports of approximately 30% extensively skewed or monoallelic methylation, in agreement with likely age-related deregulated methylation of the HUMARA gene locus. We conclude that the transcriptionally based X-chromosome clonality assays are suitable for evaluation of clonal hematopoiesis in elderly women. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Does HUMARA assay for assessment of clonal hematopoiesis have shortcomings? Neeraj Agarwal, Roberto H. Nussenzveig, Sabina I. Swierczek, Charles J. Parker, and Josef T. Prchal Blood 2009 114: 2357-2358. [Full Text] [PDF] Response: To be skewed or not to be? This is no longer the question Lambert Busque, Yves Paquette, Luigina Mollica, Denis-Claude Roy, Ross L. Levine, and D. Gary Gilliland Blood 2009 114: 2358-2359. [Full Text] [PDF] Good news for the aging population? Paresh Vyas and Douglas R. Higgs Blood 2008 112: 3001. [Full Text] [PDF] This article has been cited by other articles: N. Agarwal, R. H. Nussenzveig, S. I. Swierczek, C. J. Parker, and J. T. Prchal Does HUMARA assay for assessment of clonal hematopoiesis have shortcomings? Blood, September 10, 2009; 114(11): 2357 - 2358. [Full Text] [PDF] L. Busque, Y. Paquette, L. Mollica, D.-C. Roy, R. L. Levine, and D. G. Gilliland Response: To be skewed or not to be? This is no longer the question Blood, September 10, 2009; 114(11): 2358 - 2359. [Full Text] [PDF] L. Busque, Y. Paquette, S. Provost, D.-C. Roy, R. L. Levine, L. Mollica, and D. Gary Gilliland Skewing of X-inactivation ratios in blood cells of aging women is confirmed by independent methodologies Blood, April 9, 2009; 113(15): 3472 - 3474. [Abstract] [Full Text] [PDF]

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