RECOMBINANT HUMAN INTERFERON-ALPHA, INTERFERON-BETA AND INTERFERON-GAMMA REDUCE THE ANTIPROLIFERATIVE ACTION OF CYTARABINE IN K562 HUMAN MYELOID-LEUKEMIA CLONOGENIC CELLS

The effects of recombinant human interferons-alpha, beta and gamma (IFN) on the antiproliferative activity of cytarabine in K562 human myeloid leukaemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN-alpha did not affect the antiproliferative activity of cytarabine in K562 cultures treated with low concentrations of cytarabine (10-50 nM), whereas in those treated with high concentrations (100-150 nM) IFN-alpha increased the IC50 of cytarabine on day 5 from 102 nM to 214 nM, i.e., cytarabine combined with IFN-alpha was about two-fold less potent than cytarabine alone. Similarly, low concentrations of IFN-beta and IFN-gamma did not affect the antiproliferative activity of cytarabine on K562 colonies, but high concentrations of these two interferons: 4 x 10(3) U/ml and 10(4) U/ml respectively, increased the IC50 of cytarabine on day 5 to 304 nM and to 316 nM respectively, i.e. cytarabine combined with IFN-beta or IFN-gamma was about threefold less potent than cytarabine alone. The evaluation of the present negative interactions of interferons with cytarabine is warranted in fresh cells from myeloid leukaemia patients in primary culture.