13cis- and all-trans retinoic acid have antiproliferative effects on CML cells and render IFN alpha antiproliferative potency after combined treatment in vitro.

The treatment of CML with IFN alpha is limited due to resistance against this substance. Recent studies with different cells than chronic myelogenous leukemic cells revealed a synergistic effect of a combined use of Retinoids (RA) and IFN alpha. The purpose of the study was to detect possible interactions of IFN alpha and RA in CML considering also the effect of the BCR-ABL gene-product. Therefore, we investigated three CML cell lines in their proliferation after incubation with IFN alpha and Retinoids alone and in combination. We measured low susceptibility to IFN alpha but a marked influence of the Retinoids. In combination, the growth inhibition was enhanced potentially in response to an increased efficacy of IFN alpha. Even solely, ineffective concentrations of both substances lead to decreased proliferation.