Endogenous interleukin-1 can regulate the autonomous growth of the blast cells of acute myeloblastic leukemia by inducing autocrine secretion of GM-CSF.
We have studied peripheral blood blast cells from a patient with acute myeloblastic leukemia (AML) whose cells proliferated autonomously at high cell density, but only in the presence of adherent cells. At low cell density in suspension culture and in a clonogenic assay, blast cell growth was stimulated by recombinant granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant interleukin-1 (IL-1) independently. The response to rIL-1 was inhibited (less than 90%) by anti-GM-CSF, suggesting that the proliferative response to IL-1 was mediated by GM-CSF. This was supported by experiments which demonstrated that blast cell conditioned medium prepared in the presence of IL-1 contained GM-CSF activity which stimulated the growth of normal granulocyte-macrophage precursors (CFU-GM) and of homologous GM-CSF responsive AML blasts. As IL-1 but no GM-CSF activity was detected in BCCM prepared without exogenous IL-1 and a neutralizing antibody to IL-1 inhibited the autonomous growth of blasts in suspension culture, we conclude that the endogenous secretion of IL-1 by leukemic cells stimulated autocrine GM-CSF secretion, inducing autonomous growth of the blast cell population.
University Department of Haematology City Hospital, Nottingham, U.K.
D
D
Bradbury
G
G
Bowen
R
R
Kozlowski
I
I
Reilly
N
N
Russell
D002455:Cell Division; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor