Pro-IL-1β Processing is an Essential Step in the Autocrine Regulation of Acute Myeloid Leukaemic Cell Growth

TLDR: The study shows that autonomous growth of AML cells is inhibited by antisense oligonucleotide to IL-1β converting enzyme and by IL- 1RA, and suggests that pro-IL-1 β processing is an essential step in the regulation ofAML cell growth.

Abstract: Publisher Summary This chapter presents a study on pro-1L-1β processing in the autocrine regulation of acute myeloid leukaemic (AML) cell growth. For this study, leukaemia cells of 19 randomly selected AML patients were obtained at diagnosis from bone marrow (BM) and peripheral blood (PB) samples. Low-density leukaemia cells were prepared by using the Ficoll–Hypaque density gradient, and they were grown continuously in the presence of recombinant human IL-1RA, or phosphorothioate-derived 16-mer antisense oligonucleotide for human IL-1β converting enzyme CCT-TGT-CGG-CCA-TGG-C. The effects of the agents on AML cell growth were assessed by using two complementary systems: colony formation (CFU-AML) and AML cell proliferation. Both BM-derived and PB-derived AML cells displayed autonomous growth. Spontaneous cell proliferation varied, as well as CFU-AML colony formation, and did not correlate with the type of AML according to the FAB criteria. The study shows that autonomous growth of AML cellsis inhibited by antisense oligonucleotide to IL-1β converting enzyme and by IL-1RA. IL-1 blockade affected AML cell proliferation as well as AML cell progenitors. Since the inhibitory effect of antisense ICE oligonucleotide was more efficient when compared to the effect of IL-1RA, the results suggest that pro-IL-1β processing is an essential step in the regulation of AML cell growth.