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The influence of 2-CDA and interferon alpha (IFN-alpha) on the CFU-GM cells from ten normal individuals as well as on the CFU-GM from ten patients with chronic myeloid leukemia (CML) and on clonogenic leukemic blasts (CFU-L) from ten patients with acute myeloid leukemia (AML) in semi-solid cultures in vitro was investigated. The agents were added to the cultures alone and in combinations at concentrations of 20, 40 and 80 nM/l of 2-CDA and 10(2), 10(3) and 10(4) U/ml of IFN-alpha. A dose-dependent growth inhibition of CFU-GM as well as of CFU-L was observed. The inhibitory effect of both drugs used alone was significantly greater on the CFU-GM cells from patients with CML than on cells from normal donors. However, 2-CDA and IFN-alpha used together showed greater additive effect on the CFU-L than on the CFU-GM from normal donors and from CML patients.

We investigated the influence of TNF alpha and its muteins III, V and VI on the colony growth of normal and CML CFU-GM cells as well as on CFU-L clonogenic blasts from AML patients in cultures in vitro. The muteins were constructed using a synthetic cDNA fragment substituting nucleotides coding for the N-terminal amino acids in the chain of native TNF alpha. We observed that TNF alpha and mutein VI inhibited the growth of colonies formed by both types of CFU-GM and CFU-L cells in a greater degree than muteins III and V. In addition, the percentage of colony growth inhibition after the use of mutein VI was the greatest. These observations were the basis for the evaluation of interaction between 2-CdA and TNF alpha and between 2-CdA and mutein VI. We have confirmed that 2-CdA used together with mutein VI acts synergistically on CFU-GM and CFU-L cells, whereas 2-CdA and TNF alpha show the additive effect.