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Apoptosis

Interleukin-1β maintains an apoptosis-resistant phenotype in the blast cells of acute myeloid leukaemia via multiple pathways

Leukemia volume 18, pages 1662–1670 (2004)Cite this article

Abstract

Blast cell survival in suspension culture is associated with chemoresistance in acute myeloid leukaemia (AML). Autonomous production of IL-1β by AML blasts is linked with a proliferative response, although its role in survival and hence apoptosis-resistance has not been examined in this disease. Cells that secreted more than 19.7 pg/ml IL-1β were significantly more resistant to spontaneous apoptosis in 48-h culture than those that produced less than 19.7 pg/ml IL-1β (P=0.008). Exogenous rhIL-1β significantly enhanced 48-h survival in 25/29 blast cell samples (P=0.0001). IL-1 receptor ligation is known to activate at least three survival pathways: those mediated by PI-3 kinase, IL-1 receptor-associated kinase (IRAK) and ceramidase. In apoptosis-sensitive AML blasts with a strong survival response to rhIL-1β, inhibitors of all three pathways down-modulated an IL-1β-mediated increase in blast survival, but only the inhibition of all three pathways totally eliminated viable blasts. In apoptosis-resistant and apoptosis-sensitive primary AML samples, the three inhibitors all increased apoptosis in vitro after 48 h. Exogenous rhIL-1β induced the hyperphosphorylation of Bcl-2. It also increased the activation of NF-κB in 5/15 blast samples. IL-1β-mediated survival pathways may be a factor in apoptosis-resistance in primary AML blasts, and may therefore contribute to chemoresistance.

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Authors and Affiliations

  1. Division of Haematology, University of Nottingham and Nottingham City Hospital, Nottingham, UK

    J Turzanski, M Grundy, N H Russell & M Pallis

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Correspondence to M Pallis.

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Turzanski, J., Grundy, M., Russell, N. et al. Interleukin-1β maintains an apoptosis-resistant phenotype in the blast cells of acute myeloid leukaemia via multiple pathways. Leukemia 18, 1662–1670 (2004). https://doi.org/10.1038/sj.leu.2403457

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