Effect of TPA on fructose 2,6-bisphosphate levels and protein kinase C activity in B-chronic lymphocytic leukemia (B-CLL).
Normal B lymphocytes and peripheral mononuclear blood cells from B-chronic lymphocytic leukemia (B-CLL) patients were incubated in the presence of the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In normal B lymphocytes and lymphocytes from five patients with B-CLL, TPA stimulation increased lymphocyte fructose 2,6-bisphosphate (fructose 2,6-P2) content and activity of 6-phosphofructo 2-kinase (PFK-2), which is the enzyme that catalyzes the synthesis of fructose 2,6-P2. This effect was evident after 6 h and maximal after 12-24 h of TPA exposure. In three patients, lymphocytes seemed to be refractory to TPA stimulation in the conditions described here. Lymphocyte stimulation by TPA was associated with the translocation of protein kinase C (PKC) from the soluble to the particulate membrane fraction, except in B-CLL lymphocytes refractory to the TPA effect. These results give further support to the existence within B-CLL of subsets of cells which are refractory to the stimulation by TPA and demonstrate that the tumor promoter TPA induces important metabolic changes in lymphocytes of some patients with B-CLL.
Colomer
D
D
Haematology Laboratory Department, Hospital Clínic i Provincial, Faculty of Medicine, Barcelona, Spain.
Vives Corrons
J L
JL
Bartrons
R
R
D001402:B-Lymphocytes / Q000378:metabolism*; D005635:Fructosediphosphates / Q000378:metabolism*; D006801:Humans; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D005635:Fructosediphosphates; D007773:Lactates; D019344:Lactic Acid; C027652:fructose 2,6-diphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate