Screening for induction of differentiation and toxicity to blast cells by chemotherapeutic compounds in human myeloid leukemia.

Bone marrow cells from 9 patients with acute myeloid leukemia and 1 patient with a blast crisis of chronic myeloid leukemia were cultured to determine their ability to be induced to differentiate by different chemotherapeutic compounds. Five of these 10 patients showed differentiation to granulocytic and/or monocytic cells by culture with medium containing the myeloid cell differentiation-inducing protein MGI-2. Actinomycin D induced differentiation in cells from 2 of the patients who did not show differentiation with MGI-2 containing medium. In these 7 patients there was an increase in the ratio of differentiated myeloid cells to blasts. None of these 10 patients showed induction of differentiation by cytosine arabinoside, adriamycin, or daunomycin, but treatment with these compounds showed in some patients an increase in the ratio of differentiated myeloid cells to blasts. The results indicate that this ratio can be increased by differentiation and also in some patients by toxicity to blast cells. With dexamethasone or vinblastine there was no induction of differentiation and no increase in this ratio in any of the 10 patients tested. After in vivo chemotherapy with low dose cytosine arabinoside, cells from one patient showed a similar response in culture to actinomycin D as cells before chemotherapy, whereas in another patient the cells had acquired the ability to respond to actinomycin D. In contrast, after high-dose in vivo chemotherapy with cytosine arabinoside and daunomycin, cells from a third patient seemed to have lost the ability to differentiate in vitro by MGI-2 containing medium or actinomycin D. The results indicate that pre-screening for differentiation-inducing compounds and compounds that show toxicity to blast cells should be useful to select the appropriate compounds to be used for therapy, and that it is advisable to screen the cells both before and after initiation of therapy.