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Interleukin‐1 and interleukin‐2 control granulocyte‐ and granulocyte‐macrophage colony‐stimulating factor gene expression and cell proliferation in cultured acute myeloblastic leukemia
Author(s) -
Cozzolino Federico,
Torcia Maria,
Bettoni Stefania,
Aldinucci Donatella,
Burgio Vito L.,
Petti Maria C.,
Rubartelli Anna,
Barbui Tiziano,
Rambaldi Alessandro
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910460525
Subject(s) - acute myeloblastic leukemia , granulocyte macrophage colony stimulating factor , cytokine , autocrine signalling , cell growth , biology , granulocyte colony stimulating factor , granulocyte , immunology , microbiology and biotechnology , cell culture , leukemia , medicine , biochemistry , genetics , chemotherapy
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) I. In parallel, blasts from 5 of these patients were studied for granulocyte‐macrophage colonystimulating factor (GM‐CSF) or granulocyte‐CSF (G‐CSF) mRNA. IL‐I 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‐I‐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‐I also increased the levels of GM‐CSF protein synthesis. Addition of neutralizing anti‐IL‐I antibodies to AML cell cultures completely abolished ongoing GM‐CSF synthesis, suggesting that endogenous IL‐I is needed to maintain autocrine production of CSFs. The effects of rlL‐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 I 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.