Differentiation inducing agents in double and triple combinations can induce differentiation in primary culture of more than 80% of blast cells from some AML patients. In the present study, the interactions between these differentiating agents have been analysed using Berenbaum's general algebraic solution and three new, potentially clinically useful synergistic combinations: have been identified all trans retinoic acid (RA) + hexamethylene bisacetamide (HMBA), cytosine arabinoside (Ara-C) + HMBA and RA + Ara-C + HMBA. A measure of the effectiveness of these combinations was that the doses of Ara-C and HMBA required to induce 50% differentiation were decreased about 10-fold and 5-fold, respectively, in combination with 1 microM RA. The new synergistic combinations are important not only to limit toxicity but also because multiple drug combinations may better overcome the inherent molecular heterogeneity of the differentiation defect in AML patients. They warrant clinical trial in AML patients who are either unsuitable for or are unresponsive to conventional cytotoxic chemotherapy.

Plasma cholesterol concentrations were determined in 83 acute myeloid leukemia patients. Mean plasma cholesterol concentration (+/- S.D.) at the time of diagnosis was 2.91 mmol/L (+/- 1.13). The percentage of AML patients having hypocholesterolemia was 90.4 per cent. The lowest cholesterol levels were observed in the poorly differentiated FAB subtypes of acute myeloid leukaemia: AMyL(M1) and AMoL(M5a). The results showed that the initial hypocholesterolemia in acute myeloid leukemia is significantly related to the degree of both cytological and cytochemical maturation of leukemic blast cells at diagnosis. The degree of maturation at diagnosis has been shown to be related to prognosis in favour of more differentiated subtypes of acute myeloid leukemia. Also, hypocholesterolemia has been shown in several epidemiological studies to be related to an increased mortality from human cancer. Therefore, the degree of maturation may serve as a link between hypocholesterolemia and the increased mortality from human cancer.

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The network of interactions between human myelopoietic growth factors can lead to signal amplification that all regulate normal myelopoiesis. The present study identified synergistic interactions between recombinant human interleukin-3, GM-CSF and G-CSF on normal human marrow day 14 CFU-GM suggesting that the interactions between these human myelopoietic growth factors are mainly confined to the early stages of normal human myelopoiesis. The synergistic combinations of recombinant human interleukin-3 plus G-CSF and GM-CSF plus G-CSF warrant clinical trial for the recovery from cancer chemotherapy or radiotherapy-induced myelosuppression and for augmenting human defence against infections.