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.

journal_name

Leukemia

journal_title

Leukemia

authors

Lajmanovich A,Berthier R,Schweitzer A,Leger J,Hollard D

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

1211-8

issue

8

eissn

0887-6924

issn

1476-5551

journal_volume

7

pub_type

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