title: Constitutive expression of GM-CSF mRNA by CML blast cells is correlated with endogenous megakaryocytic colony formation.
abstract: Purified blast cells from peripheral blood of 12 patients, with chronic myelogenous leukemia (CML) in chronic phase, were analyzed for the constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) transcript. Seven out 12 patients exhibited the specific 1.0 kb GM-CSF mRNA. Six from these patients presented an increased level of spontaneous megakaryocytic colony formation. Using an immunocytochemical procedure, the presence of GM-CSF was detected in a large proportion (52% to 72%) of the blast cells of the three patients studied, who were selected for the high expression of GM-CSF mRNA transcripts. Because the role of GM-CSF in the regulation of human megakaryocytopoiesis is well documented, we investigated the inhibiting effect of anti-GM-CSF antibodies on the spontaneous megakaryocytic colony growth 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 spontaneous megakaryocytic colony growth of the same three patients. No significant inhibiting effect was observed, showing that the role of GM-CSF in the spontaneous colony formation is not mediated by IL-1. In addition, patients who constitutively expressed the GM-CSF transcript and showed endogenous megakaryocytic colony growth were those having a significantly higher platelet count than the group of patients without GM-CSF transcript and with no endogenous megakaryocytic colonies. In conclusion, these results suggest that GM-CSF, but not IL-1, participates in the production of spontaneous megakaryocytic colony formation observed in some CML patients. The true autocrine or paracrine nature of this stimulation remains to be established.
authors.affiliation: Centre Hospitalier Regional Universitaire de Grenoble, Unité d'Hématologie Expérimentale, France.
authors.forename: A
authors.initials: A
authors.lastname: Lajmanovich
authors.forename: R
authors.initials: R
authors.lastname: Berthier
authors.forename: A
authors.initials: A
authors.lastname: Schweitzer
authors.forename: J
authors.initials: J
authors.lastname: Leger
authors.forename: D
authors.initials: D
authors.lastname: Hollard
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008533:Megakaryocytes / Q000473:pathology*; D010976:Platelet Count; D012333:RNA, Messenger / Q000097:blood*; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor