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 biological effects through occupancy of its receptor (G-CSFR). WEHI-3B D- myelomonocytic 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 D3 by the formation of mature cells. Transfection of the G-CSFR gene into WEHI-3B D- cells resulted in three major changes. G-CSFR-expressing clones (a) acquired the capacity to respond 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 transfected with vector alone behaved like parental WEHI-3B D- cells. The findings imply that the near diploid phenotype is required for WEHI-3B D- leukemia cells to respond to certain inducers of differentiation.