title: Coexpression of the genes for interleukin 6 and its receptor without apparent involvement in the proliferation of acute myeloid leukemia cells.
abstract: Leukemic cells isolated from patients with either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) were screened for their capacity to express the interleukin 6 (IL-6) and IL-6 receptor genes, both at the RNA and protein levels. Variable levels (10 to greater than 600 U/ml) of an IL-6 activity, inhibited by neutralizing anti-IL-6 antibodies, were detected in AML cell supernatants using the B9 cell bioassay. High levels (greater than 100 U/ml) were observed in differentiated (M4 and M5 stages) AML, as well as in less mature (M1 and M2 stages) AML. Detection of the IL-6 transcript correlated with the biological activity. In addition, both IL-6 activity and IL-6 mRNA were detected in "fresh" leukemic cells, indicating that the glycoprotein was actually synthesized in vivo. In contrast, the IL-6 gene was less frequently expressed in ALL. The IL-6 receptor gene was transcribed in both AML and ALL; binding experiments showed that the protein was present at the cell surface. The spontaneous in vitro proliferation of leukemic cells coexpressing the transcripts for IL-6 and its receptor was not significantly inhibited by a neutralizing anti-IL-6 antibody, suggesting that IL-6 is not primarily implicated in the proliferation of the leukemic clone via an autocrine loop. Synthesis of IL-6 could, however, confer on leukemic cells a selective growth advantage through activation of the cytokine cascade.
authors.affiliation: Cancérologie et Thérapeutique Expérimentales, U 119 de l'INSERM, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: N
authors.initials: N
authors.lastname: Maroc
authors.forename: F
authors.initials: F
authors.lastname: Kerangueven
authors.forename: F
authors.initials: F
authors.lastname: Bardin
authors.forename: M
authors.initials: M
authors.lastname: Courcoul
authors.forename: C
authors.initials: C
authors.lastname: Lavezzi
authors.forename: F
authors.initials: F
authors.lastname: Birg
authors.forename: P
authors.initials: P
authors.lastname: Mannoni
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D015152:Blotting, Northern; D002455:Cell Division; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D019947:Receptors, Interleukin-6; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D003470:Culture Media; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6