Interleukin-1 and interleukin-2 control granulocyte- and granulocyte-macrophage colony-stimulating factor gene expression and cell proliferation in cultured acute myeloblastic leukemia.
In vitro proliferation of leukemic cells purified from 10 cases of acute myeloblastic leukemia (AML) was analyzed in basal conditions or in the presence of exogenous recombinant (r) Interleukin (IL) 1. In parallel, blasts from 5 of these patients were studied for granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF) mRNA. IL-1 augmented the spontaneous AML cell proliferation in all cases and induced de novo expression or increased amounts of GM-CSF and/or G-CSF transcripts in 4 of the 5 cases evaluated. IL-1-induced AML cell proliferation was modulated by neutralizing anti-GM-CSF or anti-G-CSF antibodies in those cases in which CSF mRNAs were induced or increased by exogenous cytokine. In the same cases, biosynthetic labelling and immunoprecipitation studies using monospecific anti-GM-CSF antibodies showed that IL-1 also increased the levels of GM-CSF protein synthesis. Addition of neutralizing anti-IL-1 antibodies to AML cell cultures completely abolished ongoing GM-CSF synthesis, suggesting that endogenous IL-1 is needed to maintain autocrine production of CSFs. The effects of rIL-2 were investigated in a larger series of 21 patients. The cytokine reduced spontaneous AML cell proliferation in 8 cases. It caused complete disappearance of GM-CSF mRNA in 1 case, and marked reduction of G-CSF mRNA in 2 cases. Increased AML cell proliferation was observed in 2 of 21 cases. These findings suggest that expression of CSF genes and cell proliferation in AML are under the control of different cytokines acting in autocrine or paracrine fashion.
Istituto di Clinica Medica IV, University of Florence, Italy.
F
F
Cozzolino
M
M
Torcia
S
S
Bettoni
D
D
Aldinucci
V L
VL
Burgio
M C
MC
Petti
A
A
Rubartelli
T
T
Barbui
A
A
Rambaldi
D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor