Suppression of juvenile chronic myelogenous leukemia colony growth by interleukin-1 receptor antagonist

R. Schiro, D. Longoni, V. Rossi, O. Maglia, A. Doni, M. Arsura, G. Carrara, G. Masera, E. Vannier, C. A. Dinarello, A. Rambaldi, A. Biondi

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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-1β (IL-1β), and tumor necrosis factor alpha (TNFα) 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-1Ra) 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-1β-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-1β-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-1β in the pathogenesis of JCML and suggest that the use of IL-1Ra could represent a novel therapeutic strategy against this disorder.

Original languageEnglish
Pages (from-to)460-465
Number of pages6
Issue number2
Publication statusPublished - Jan 15 1994

ASJC Scopus subject areas

  • Hematology


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