THE ROLE OF DNA-PLOIDY IN THE DIFFERENTIATION OF WEHI-3B D- LEUKEMIA-CELLS TRANSFECTED WITH THE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR GENE

Granulocyte colony-stimulating factor (G-CSF) exerts various biologica l effects through occupancy of its receptor (G-CSFR). WEHI-3B D- myelo monocytic leukemia cells do not express the G-CSFR, do not respond to G-CSF or to retinoic acid by the induction of granulocytic maturation, contain a near tetraploid content of DNA, and form tightly aggregated colonies. However, they still maintain the capacity to differentiate since they respond to vitamin Ds by the formation of mature cells. Tra nsfection of the G-CSFR gene into WEHI-3B D- cells resulted in three m ajor changes. G-CSFR-expressing clones (a) acquired the capacity to re spond to the differentiation-inducing properties of G-CSF and retinoic acid, (b) formed colonies which exhibited a dispersed phenotype, and (c) exhibited near diploid DNA ploidy. In contrast, WEHI-3B D- cells t ransfected with vector alone behaved like parental WEHI-3B D- cells. T he findings imply that the near diploid phenotype is required for WEHI -3B D- leukemia cells to respond to certain inducers of differentiatio n. (C) 1995 Academic Press, Inc.