CD133 (AC133) expression on AML cells and progenitors.
BACKGROUND
AML blasts differ in their functional capability, creating a hierarchy of progenitors. CD133 (AC133) is a newly described transmembrane protein expressed on CD34(+) and CD34(-) normal progenitors. We characterized the prognostic significance of CD133 expression in AML and expression of CD133 on AML progenitors thought to be responsible for maintaining this disease.


METHODS
AML cells from 102 patients were analyzed for CD133 and CD34 expression, and correlated with outcome in 92 treated patients. AML cells were also FACS sorted into CD34(+)/CD133(+), CD34(+)/CD133(-), CD34(-)/CD133(+) and CD34(-)/CD133(-) subfractions, and assayed in vitro in colony-forming assay (CFU) and in suspension culture (SC) assay for up to 8 weeks, and in vivo in non-obese diabetic (NOD)/SCID mice to determine the phenotype of progenitors detected in these assays.


RESULTS
CD133 expression was not correlated with event-free or overall survival, FAB subtype, cytogenetic abnormality or WBCC, but was correlated with CD34 expression. Primary AML CFU were present in all four sorted fractions. After an increasing period of time in SC, a higher proportion of cells capable of forming leukemic CFU were found in the CD34(+)/CD133(+) subfraction. Cells capable of producing leukemic engraftment in NOD/SCID mice were found in all subfractions, including the CD34(-)/CD133(-) subfraction in many patients.


CONCLUSIONS
CD133 is not useful as a prognostic marker in AML. CD133 is expressed with CD34 on most primitive leukemic progenitors detected in vitro, however, in vivo progenitors could not be purified using CD133 in these patients.
Vercauteren
S M
SM
Terry Fox Laboratory, British Columbia Cancer Agency Vancouver Hospital and Health Sciences Centre, Vancouver, BC Canada.
Sutherland
H J
HJ
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002469:Cell Separation; D017690:Cell Transplantation; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis
D015703:Antigens, CD; D008565:Membrane Proteins