title: Functional and phenotypic upregulation of CD13/aminopeptidase-N on precursor-B acute lymphoblastic leukemia after in vitro stimulation.
abstract: Acute lymphoblastic leukemia (ALL) cells of precursor-B type were assessed for expression of the cell surface peptidase CD13 (aminopeptidase-N) after 72 hours' culture in 10% B cell growth factor (BCGF), TPA, or medium alone. CD13 was analyzed phenotypically using a specific monoclonal antibody (mAb) by flow cytometry, and also with a spectrophotometric enzyme assay to measure the cleavage of specific peptide substrates. CD13 antigen was induced in all 10 cases of precursor-B ALL after culture with BCGF, with weaker expression seen in cells incubated with TPA or in medium alone. Aminopeptidase-N-like enzymatic activity was also demonstrated in cultured cells, particularly after BCGF exposure. Using the mAb WM-15, which specifically inhibits aminopeptidase-N function, we demonstrated that induction of true aminopeptidase-N activity was largely restricted to BCGF-treated cells, in which approximately 20% of total aminopeptidase activity was due to aminopeptidase-N. Phenotypic expression of the peptidase CD10 (neutral endopeptidase) was not altered on cultured cells. These findings indicate that CD13 expression can be selectively upregulated on ALL cells in response to proliferative stimuli. This peptidase, in cooperation with CD10 and perhaps other surface enzymes, may act to regulate the concentration of molecules at the cell surface which influence the growth of precursor-B ALL cells.
authors.affiliation: Department of Haematology, Westmead Hospital, New South Wales, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Makrynikola
authors.forename: E J
authors.initials: EJ
authors.lastname: Favaloro
authors.forename: T
authors.initials: T
authors.lastname: Browning
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: K F
authors.initials: KF
authors.lastname: Bradstock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D001752:Blast Crisis; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D018826:CD13 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015847:Interleukin-4; D018826:CD13 Antigens; D013755:Tetradecanoylphorbol Acetate