title: Growth potentiating activity of endogenous production of interleukin-1 and tumor necrosis factor alpha in blast cells of acute myeloblastic leukemia.
abstract: For the optimal growth of clonogenic cells in acute myeloblastic leukemia (AML), several cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 are required in addition to colony-stimulating factor (CSF), which may be produced by blast cells themselves. In the present study, we addressed the potential role of endogenous production of TNF-alpha and/or IL-1 in the in vitro growth of AML clonogenic cells supported by IL-3. Addition of a specific neutralizing antibody against TNF-alpha (anti-TNF-alpha) to the culture significantly reduced the growth-stimulating effect of IL-3 on the cells in 11 of 14 patients. Simultaneous addition of anti-IL-1 alpha and anti-IL-1 beta also partly affected the growth, although to a much lesser extent when compared to the effect observed with anti-TNF-alpha. In 3 patients, the growth-stimulating effect of IL-3 was completely abrogated by anti-TNF-alpha or a combination of all three antibodies. Constitutive TNF-alpha transcript was observed in 5 patients and TNF-alpha protein was present in culture supernatant. Following in vitro culture, a transient but profound increase in c-fos, c-jun, TNF-alpha and IL-1 beta mRNA levels was observed. Anti-TNF-alpha inhibited the accumulation of TNF-alpha transcript, suggesting that membrane-integrated TNF-alpha may be partly responsible for the induction of TNF-alpha mRNA. It seems likely that the accumulation of these genes occurs through a protein kinase C-independent signaling pathway.
authors.affiliation: Department of Laboratory Medicine, Tokyo Medical and Dental University, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Murohashi
authors.forename: S
authors.initials: S
authors.lastname: Tohda
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: Y
authors.initials: Y
authors.lastname: Hirai
authors.forename: N
authors.initials: N
authors.lastname: Nara
mesh_terms: D000906:Antibodies; D002455:Cell Division; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D007377:Interleukin-3; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha