IL-2 INHIBITS PROLIFERATION OF K562 CELLS AND REDUCES ACCUMULATION OFBCR ABL MESSENGER-RNA AND ONCOPROTEIN/

Cell lines of myeloid origin have been shown to express interleukin-2 receptors (IL-2R). Here, we demonstrate the expression of IL-2R alpha and IL-R beta on the CML blast cell line K562 by FAGS analysis and cro ss-linking assay. Furthermore, we examined the effect of IL-2 on leuke mic progenitor growth, employing K562 as a model. Clonogenic growth wa s assessed after 3 days of culture by colony formation in a serum-free , semi-solid assay system. IL-2 was found to exhibit a dose-dependent suppressive effect on K562 clonogenicity with 48% inhibition of colony formation at 250 U IL-2 and 60% inhibition at 1000 U IL-2. Philadelph ia chromosome (Ph)-positive K562 cells possess multiple copies of the bcr/abl fusion gene whose transcript and protein product (p210) is tho ught to confer growth advantage to CML cells. We therefore investigate d IL-2-dependent modulation of bcr/abl mRNA accumulation and p210 prot ein levels in K562 cells. After 4 h of culture in the presence of IL-2 , a 3-15-fold reduction of bcr/abl mRNA accumulation was demonstrated by competitive reverse PCR. Reduction of bcr/abl fusion protein levels was demonstrated at 24 h of IL-2-supplemented cell culture, employing p210 recognizing monoclonal antibodies (mAbs) in FAGS analysis. Level s of proliferation marker Ki67 were only marginally affected. We concl ude: (1) K562 cells express both IL-2R alpha and IL-R beta; (2) IL-2 i nhibits clonogenic growth of K562 in a dose-dependent manner; and (3) IL-2-mediated inhibition of K562 proliferation is preceded by a reduct ion of bcr/abl mRNA accumulation and p210 protein levels.