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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1010-1015. Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-04-1498.
Submitted April 26, 2004
Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA * Corresponding author; email: Dunbarc{at}nhlbi.nih.gov.
Due to high frequency of side effects caused by high dose total body irradiation (TBI) the non-myeloablative regimen together with cytotoxic agents is currently used especially for elderly patients. However, immediate and long-term effects of low dose irradiation employed in allogeneic transplantation on stem cells is less well known. We have studied the effect of low dose 3 Gy TBI on the number of hematopoietic stem cell (HSC) clones contributing simultaneously to granulocyte production in rhesus macaque. The number of clones post-3 Gy TBI decreased markedly by 2-3 weeks post-3 Gy TBI, followed by a period of clonal instability, and recovery to almost pre-3 Gy TBI clonal diversity. The clones accounting for this recovery contributed pre-3 Gy TBI, suggesting the profound initial impact of TBI was on a pool of progenitor cells, where as most of the more primitive HSCs remained unaffected and were able to regain contributing to hematopoiesis after recovery. Clonal fluctuation may indirectly suggest the presence of short term/long term HSC populations in rhesus macaque bone marrow as reported in a mouse model. The results indicate that even low dose irradiation affects hematopoietic clonal dynamics, and have implications for design of conditioning regimens for transplantation purposes.
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