Rapid morphological and substratum adherence response by hairy cell and other human leukemic cells to phorbol ester...

Human leukemic cells, maintained in tissue culture, responded differentially following exposure to the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). Short-term (0-2 h) TPA treatment of hairy cell leukemic cells (of presumed B-lymphocytic origin) resulted in the attachment of 5-100% of cells (depending on % leukemic mononuclear cells) to the culture dish and extension of long processes. Similar changes were also observed with cells from acute myelogenous, acute prolymphocytic and some acute monomyelocytic leukemic patients. Related non-promoters such as phorbol and 4-alpha-phorbol-12, 13-didecanoate, had no effect. In contrast, both chronic and acute lymphocytic, chronic myelogenous and acute promyelocytic leukemic cells showed no response to TPA over this short time period. Neither the adherence nor morphological changes were blocked by inhibitors of protein synthesis (cycloheximide) or glycosylation (tunicamycin), but the process formation was sensitive to inhibitors of microtubule formation such as colchicine. The effect was not reversible by TPA removal, and exposure to TPA for only 5 min resulted in a complete adherence and morphological induction within 60 min.