Pre-B and non-T/non-B leukemia cell lines BV-173, KM-3, NALM-6, and REH: changes in isoenzyme profiles during induction of differentiation.
The ability of 12-O-tetradecanoylphorbol 13-acetate (TPA) to induce stable phenotypic changes that serve as markers of differentiation was examined in the non-T/non-B leukemia cell lines KM-3 and REH and in the pre-B leukemia cell lines BV-173 and NALM-6. Isoenzymes of the enzymes carboxylic esterase, acid phosphatase, hexosaminidase, and lactate dehydrogenase (LDH), separated by isoelectric focusing on horizontal polyacrylamide thin-layer gels, were used to monitor induced changes. TPA in different concentrations completely or partially inhibited cell proliferation, but had no drug-related cytotoxicity. No increase in the number of nitro-blue-tetrazolium-reducing cells nor adherence to plastic surface was found. In all four cell lines, TPA caused an increase in number and staining intensity of esterase, acid phosphatase, and LDH isoenzymes. The resulting isoenzyme profiles corresponded to those seen at more mature intermediate stages of B-cell proliferation, but did not indicate a terminal differentiation to mature B cells. The loss of the hexosaminidase I isoenzyme, which is a marker of immature hematopoietic cells, was a further indicator of induced maturation. These results demonstrate that while TPA is capable of inducing various immature non-T/non-B and pre-B cell lines to differentiate, the differentiation progression appears to be restricted to intermediate stages, in contrast to the terminal differentiation inducible in myeloid cells.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology / Q000473:pathology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D008214:Lymphocytes / Q000201:enzymology / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000135:Acid Phosphatase; D000118:Acetylglucosaminidase; D013755:Tetradecanoylphorbol Acetate