Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples.
Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme that is responsible for the oxidation of intracellular aldehydes. Elevated levels of ALDH have been demonstrated in murine and human progenitor cells compared with other hematopoietic cells, and this is thought to be important in chemoresistance. A method for the assessment of ALDH activity in viable cells recently has been developed and made commercially available in a kit format. In this study, we confirmed the use of the ALDH substrate kit to identify cord blood stem/progenitor cells. Via multicolor flow cytometry of cord blood ALDH+ cells, we have expanded on their phenotypic analysis. We then assessed the incidence, morphology, phenotype, and nonobese diabetic/ severe combined immunodeficiency engraftment ability of ALDH+ cells from acute myeloid leukemia (AML) samples. AML samples had no ALDH+ cells at all, an extremely rare nonmalignant stem/progenitor cell population, or a less rare, leukemic stem cell population. Hence, in addition to identifying nonmalignant stem cells within some AML samples, a high ALDH activity also identifies some patients' CD34+/ CD38- leukemic stem cells. The incidence of normal or leukemic stem cells with an extremely high ALDH activity may have important implications for resistance to chemotherapy. Identification and isolation of leukemic cells on the basis of ALDH activity provides a tool for their isolation and further analysis.
Pearce
Daniel J
DJ
Hematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Taussig
David
D
Simpson
Catherine
C
Allen
Kirsty
K
Rohatiner
Ama Z
AZ
Lister
T Andrew
TA
Bonnet
Dominique
D
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002478:Cells, Cultured; D005312:Fetal Blood / Q000201:enzymology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D008562:Membrane Glycoproteins; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology
D015703:Antigens, CD; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D000444:Aldehyde Dehydrogenase; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1