THE INFLUENCE OF RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA AND ITS MUTEINS USED ALONE OR IN COMBINATION WITH 2-CHLORODEOXYADENOSINE ON NORMAL AND LEUKEMIC HEMATOPOIESIS IN-VITRO

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 C FU-L clonogenic blasts from AML patients in cultures in vitro. The mut eins were constructed using a synthetic cDNA fragment substituting nuc leotides coding for the N-terminal amino acids in the chain of native TNF alpha. We observed that TNF alpha and mutein VI inhibited the grow th of colonies formed by both types of CFU-GM and CFU-L cells in a gre ater degree than muteins III and V. In addition, the percentage of col ony growth inhibition after the use of mutein VI was the greatest. The se observations were the basis for the evaluation of interaction betwe en 2-CdA and TNF alpha and between 2-CdA and mutein VI. We have confir med that 2-CdA used together with mutein VI acts synergistically on CF U-GM and CFU-L cells, whereas 2-CdA and TNF alpha show the additive ef fect. (C) 1997 Elsevier Science Ltd.