NOD/SCID mice transplanted with marrow from patients with myelodysplastic syndrome (MDS) show long-term propagation of normal but not clonal human precursors.
Sublethally irradiated NOD/SCID mice were transplanted with hematopoietic progenitor cells obtained from the marrow of patients with myelodysplastic syndromes (MDS). Engraftment of MDS cells, as determined by flow cytometry, was delayed compared to marrow from normal donors. Human CD38(+)CD34(-) cells were prominent in marrows and spleens of MDS chimeras. CD34(+)CD38(-), CD34(+)CD38(+) and T cells were also easily detected. Human myeloid cells (CD33(+); CD15(+)) were present in low proportions. No clonal precursors were identified by fluorescent in situ hybridization (FISH) or by molecular analysis of polymorphic X-linked markers in mice with documented engraftment of human cells more than 2 months after transplantation. These data indicate that human cells present in murine MDS chimeras, at the levels of sensitivity of our assays, were derived from residual normal cells in human MDS marrow, and suggest that the NOD/SCID environment was not conducive to the expansion of clonal MDS precursors. This model may allow identification of factors relevant for sustaining or expanding clonal precursors.
Benito
Ana I
AI
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D1-100, P.O. Box 19024, Seattle, WA 98109-1204, USA.
Bryant
Eileen
E
Loken
Michael R
MR
Sale
George E
GE
Nash
Richard A
RA
John Gass
M
M
Deeg
H Joachim
HJ
D000328:Adult; D000753:Anemia, Refractory / Q000473:pathology; D000754:Anemia, Refractory, with Excess of Blasts / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D016026:Bone Marrow Transplantation; D002648:Child; D002999:Clone Cells; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D011828:Radiation Chimera; D011944:Receptors, Androgen / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D011944:Receptors, Androgen