Effects of phenylacetate on cells from patients with B-chronic lymphocytic leukemia.
Peripheral blood mononuclear cells from 11 patients with untreated B-chronic lymphocytic leukemia (CLL) were exposed to sodium phenylacetate (NaPA) in culture to assess its ability to induce differentiation. We found no evidence of cellular differentiation or induction of tartrate resistant acid phosphatase activity, as seen when B-CLL cells were treated with phorbol ester. We observed a striking decrease in the viability of the B-CLL cells in a time and dose dependent fashion when exposed to NaPA. After six days of culture, control cells from the 11 patients studied had a median viability of 90%, whereas cells exposed to NaPA at 5 and 10 mM concentrations had median viabilities of 39 and 16%, respectively. The cells treated with NaPA developed prominent cytoplasmic vacuoles. NaPA binds and depletes glutamine which is an important amino acid for lymphocyte metabolism. Although the mechanism of the cytocidal effects demonstrated in this study are unknown, they may relate at least partially to glutamine deprivation.
Call
T G
TG
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55904.
Stenson
M J
MJ
Witzig
T E
TE
D000135:Acid Phosphatase / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014066:Palatine Tonsil / Q000166:cytology; D010648:Phenylacetates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D010648:Phenylacetates; D000135:Acid Phosphatase; C025136:phenylacetic acid