Potential pre-screening for therapeutic agents that induce differentiation in human myeloid leukemia cells

A cultured line of human myeloid leukemic cells has been used, to test for the ability of compounds used in chemotherapy to induce partial or complete differentiation of these leukemic cells. The compounds differed in their ability to induce specific differentiation-associated properties. Effectiveness of induction of Fc and C3 rosettes was of the order actinomycin C greater than cytosine arabinoside greater than mitomycin-C greater than adriamycin greater than bromodeoxyuridine greater than hydroxyurea. Induction of rosettes by actinomycin-D required a 8212-fold lower concentration than induction by hydroxyurea. All these compounds, except bromodeoxyuridine, induced the synthesis and secretion of lysozyme with the same order of effectiveness as for rosettes, but only actinomycin-D and to a lesser extent bromodeoxyuridine induced the formation of mature granulocytes. Vincristine induced only a small increase in lysozyme. The results indicate that actinomycin-D was the most potent inducer of differentiation in these human myeloid leukemic cells. It is suggested that pre-screening of individual patients for the most effective compounds that can induce differentiation of their myeloid leukemic cells in culture, may prove beneficial for treatment in a form of chemotherapy based on the induction of normal differentiation in leukemic cells.