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Suppression of juvenile chronic myelogenous leukemia colony growth by
interleukin-1 receptor antagonist [see comments]
R Schiro, D Longoni, V Rossi, O Maglia, A Doni, M Arsura, G Carrara, G Masera, E Vannier and CA Dinarello
Clinica Pediatrica Universita di Milano-H.S. Gerardo, Monza, Italy.
Bone marrow (BM) and peripheral blood (PB) cells from patients with
juvenile chronic myelogenous leukemia (JCML) exhibit spontaneous in vitro
proliferation. Several cytokines including granulocyte-macrophage
colony-stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta), and
tumor necrosis factor alpha (TNF alpha) have been implicated in supporting
the growth of leukemic monocyte-macrophage colonies either by autocrine or
paracrine pathways. In seven untreated JCML patients, we investigated the
role of IL-1 in the spontaneous growth of these cells by specifically
blocking IL-1 receptors. The IL-1 receptor antagonist (IL-1 Ra) was added
to the clonogenic assays, and in each case significant (mean = 63%, range =
35% to 82%) inhibition of spontaneous proliferation was observed.
Uncultured circulating cells from PB or BM of four out of five patients
expressed IL-1 beta-specific mRNA and secreted the protein into the culture
supernatants. Moreover, by means of reverse transcriptase-polymerase chain
reaction (RT-PCR), we demonstrated that most of the spontaneously growing
leukemic colony- forming unit cells (CFU-C) obtained from BM cells of two
patients were positive for the presence of the IL-1 beta-specific mRNA.
Despite the presence of a measurable amount of GM-CSF in JCML cell culture
supernatants, GM-CSF-specific mRNA in CFU-C cells of four cases was not
detected by RT-PCR. These data further support a central role for IL-1 beta
in the pathogenesis of JCML and suggest that the use of IL-1 Ra could
represent a novel therapeutic strategy against this disorder.
Volume 83,
Issue 2,
pp. 460-465,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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