Coexpression of the genes for interleukin 6 and its receptor without apparent involvement in the proliferation of acute myeloid leukemia cells.
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.
Lopez
M
M
Cancérologie et Thérapeutique Expérimentales, U 119 de l'INSERM, Marseille, France.
Maroc
N
N
Kerangueven
F
F
Bardin
F
F
Courcoul
M
M
Lavezzi
C
C
Birg
F
F
Mannoni
P
P
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
D015703:Antigens, CD; D018952:Antigens, CD34; D003470:Culture Media; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6