CONSTITUTIVE EXPRESSION OF GM-CSF MESSENGER-RNA BY CML BLAST CELLS ISCORRELATED WITH ENDOGENOUS MEGAKARYOCYTIC COLONY FORMATION

Purified blast cells from peripheral blood of 12 patients, with chroni c myelogenous leukemia (CML) in chronic phase, were analyzed for the c onstitutive expression of the granulocyte-macrophage colony-stimulatin g factor (GM-CSF) transcript. Seven out 12 patients exhibited the spec ific 1.0 kb GM-CSF mRNA. Six from these patients presented an increase d level of spontaneous megakaryocytic colony formation. Using an immun ocytochemical procedure, the presence of GM-CSF was detected in a larg e proportion (52% to 72%) of the blast cells of the three patients stu died, who were selected for the high expression of GM-CSF mRNA transcr ipts. Because the role of GM-CSF in the regulation of human megakaryoc ytopoiesis is well documented, we investigated the inhibiting effect o f anti-GM-CSF antibodies on the spontaneous megakaryocytic colony grow th of three of the patients expressing the GM-CSF transcript. Addition of anti-GM-CSF had a high neutralizing effect ranging from 60% to 70% inhibition of endogenous megakaryocytic colony growth. As the GM-CSF synthesis by leukemic cells is often induced by interleukin-1 (IL-1), we also investigated the effect of anti-IL-1 antibody on the spontaneo us megakaryocytic colony growth of the same three patients. No signifi cant inhibiting effect was observed, showing that the role of GM-CSF i n the spontaneous colony formation is not mediated by IL-1. In additio n, patients who constitutively expressed the GM-CSF transcript and sho wed endogenous megakaryocytic colony growth were those having a signif icantly higher platelet count than the group of patients without GM-CS F transcript and with no endogenous megakaryocytic colonies. In conclu sion, these results suggest that GM-CSF, but not IL-1, participates in the production of spontaneous megakaryocytic colony formation observe d in some CML patients. The true autocrine or paracrine nature of this stimulation remains to be established.