Human AML cells in NOD/SCID mice: engraftment potential and gene expression.
Most cases of human acute myeloid leukemia (AML) engraft in irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Intravenous transfer of as few as 10(5) human AML cells resulted in engraftment. Cases with poor prognosis clinical features, including FLT3 mutations, tended to engraft efficiently. Nevertheless, AML cells obtained from patients at relapse did not engraft more efficiently than cells obtained from the same patients at initial diagnosis. One passage of human AML cells in NOD/SCID mice did not appear to select for increased virulence, as measured by serial transplantation efficiency. Finally, cDNA microarray analyses indicated that approximately 95% of genes were expressed at similar levels in human AML cells immunopurified after growth in mice, as compared to cells assessed directly from patients. Thus, the growth of human AML cells in NOD/SCID mice could yield large numbers of human AML cells for direct experimental use and could also function as a renewable, potentially unlimited source of leukemia cells, via serial transplantation.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
R
R
Lumkul
N-C
NC
Gorin
M T
MT
Malehorn
G T
GT
Hoehn
R
R
Zheng
B
B
Baldwin
D
D
Small
S
S
Gore
D
D
Smith
P S
PS
Meltzer
C I
CI
Civin
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006085:Graft Survival; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D019718:Receptors, CXCR4 / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D019718:Receptors, CXCR4; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3