MEGAKARYOCYTIC DIFFERENTIATION OF A LEUKEMIC-CELL LINE, MC3, BY PHORBOL ESTER - INDUCTION OF GLYCOPROTEIN IIB IIIA AND EFFECTS ON EXPRESSION OF IL-6, IL-6 RECEPTOR, MPL AND GATA GENES/

We investigated megakaryocytic differentiation in a newly-established Ph(1)-positive leukemic cell line, MC3, which showed tri-lineage immun ophenotypes (myeloid antigens(2+), CD19(1+) and CD41a(1+)) and was pos itive for CD34 and CD38. TPA induced MC3 cells to differentiate to an early stage of megakaryocyte lineage exhibiting an increase in the exp ression of platelet glycoproteins (GP) IIb/IIIa (CD41a), and an increa se in cell size and nuclear ploidy. TPA treatment also enhanced the ex pression of GPIIb mRNA, and induced the expression of interleukin-6 (I L-6) and its receptor mRNAs, while it did not induce transcripts of th e genes IL-11 and mpl ligand, and further decreased the transcript of the mpl gene. Consistent with these findings, MC3 cells treated with T PA showed an increased expression of GATA-1, but not GATA-3 transcript s, whereas those without TPA treatment expressed only the GATA-2 trans cript. These results provide an insight into the study for the regulat ory mechanism of megakaryocytopoiesis and leukemic cell differentiatio n.