Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo.
Acute myeloid leukaemia (AML) is thought to be maintained by a small population of leukemic progenitor cells. To define the phenotype of such cells with long-term proliferative capacity in vitro and in vivo, we have used the production of leukemic clonogenic cells (CFU) after 2 to 8 weeks in suspension culture as a measure of these cells in vitro and compared their phenotype with that of cells capable of engrafting nonobese diabetic severe combined immune deficient (NOD/SCID) mice. Leukemic blast peripheral blood cells were evaluated for expression of CD34 and Thy-1 (CD90) antigens. The majority of AML blast cells at diagnosis lacked expression of Thy-1. Most primary CFU-blast and the CFU detected at up to 8 weeks from suspension cultures were CD34+/Thy-1-. AML cells that were capable of engrafting NOD/SCID mice were also found to have the CD34+/Thy-1- phenotype. However, significant engraftment was achieved using both CD34+/Thy-1- and CD34- subfractions from one AML M5 patient. These results suggest that while heterogeneity exists between individual patients, the leukemic progenitor cells that are capable of maintaining the disease in vitro and in vivo differ from normal hematopoietic progenitor cells in their lack of expression of Thy-1.
Blair
A
A
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver Hospital and Health Sciences Centre, Canada.
Hogge
D E
DE
Ailles
L E
LE
Lansdorp
P M
PM
Sutherland
H J
HJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001752:Blast Crisis; D002455:Cell Division; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018800:Thy-1 Antigens / Q000096:biosynthesis* / Q000097:blood; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D015703:Antigens, CD; D018952:Antigens, CD34; D018800:Thy-1 Antigens