Radiation dose determines the degree of myeloid engraftment after nonmyeloablative stem cell transplantation.
A multivariate analysis of 121 dogs conditioned with 200, 100, or 50 cGy of total body irradiation (TBI) followed by hematopoietic stem cell transplantation from matched littermates showed that TBI dose was the only factor examined that was statistically significantly associated with the percentage of donor myeloid engraftment in stable long-term chimeras ( P = .008). To understand the direct effects of low-dose irradiation on hematopoietic stem/progenitor cells, nonirradiated and irradiated human CD34 + cells were evaluated for competitive repopulating ability in nonobese diabetic/severe combined immunodeficiency beta2m -/- mice. As expected, the results showed a radiation dose-dependent loss of competitive repopulating ability. Flow cytometric analysis indicated that, within a viable cell gate, there was reduced expression of P-selectin glycoprotein ligand-1 and L selectin on irradiated compared with nonirradiated CD34 + cells; this suggests that irradiated stem/progenitor cells may be compromised in their ability to home to or interact with the marrow microenvironment. However, the CD34 + /P-selectin glycoprotein ligand-1 dim cells also showed activation of caspase-3, indicating that they were destined to die. These results suggest that the TBI dose determines the degree of myeloid engraftment by compromising the resident stem/progenitor cell compartment.
Kahl
Christoph
C
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
Mielcarek
Marco
M
Iwata
Mineo
M
Harkey
Michael A
MA
Storer
Barry
B
Torok-Storb
Beverly
B
D000818:Animals; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018598:Minisatellite Repeats; D023421:Models, Animal; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous / Q000502:physiology*; D014916:Whole-Body Irradiation
D015703:Antigens, CD; D018952:Antigens, CD34; D007166:Immunosuppressive Agents