Triple combination of retinoic acid+aclacinomycin A+ dimethylformamide induces differentiation of human acute myeloid leukaemic blasts in primary culture.

Differentiation induction therapy provides unalternative for treatment of acute myeloid leukaemia (AML) patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid(RA)+aclacinomycin A (ACM)+dimethylformamide (DMF) on differentiation of blasts from 24 AML patients was studied. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPM11640 culture medium with 20% fetal calf serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 80nM aclacinomycin A and/or 100mM dimethylformamide alone and in combinations with each other for six days at 37 degrees C in a humidified incubator under 5% CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients after exposure to the triple combination of 10(-6)M RA+80nM ACM+100mM DMF for 6 days in primary culture. These highly effective results justify a clinical trial of this triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.