Caspase-8 dependent apoptosis induction in malignant myeloid cells by TLR stimulation in the presence of IFN-alpha

• Published in: Leukemia research 2007-12, Vol.31 (12), p.1729-1735
• Main Authors: Lehner, Manfred, Bailo, Marco, Stachel, Daniel, Roesler, Wolf, Parolini, Ornella, Holter, Wolfgang
• Format: Article
• Language: English
• Subjects: AML; Apoptosis; Caspase 8 - physiology; Cell Line; Cell Line, Tumor; Hematology, Oncology and Palliative Medicine; Humans; IFN-alpha; Interferon-alpha - pharmacology; Leukemia, Myeloid, Acute - pathology; Lipopolysaccharides - pharmacology; LPS; Monocytes; Myeloid Cells; THP-1; TLR; Toll-Like Receptors - physiology
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2007.05.001

Abstract Pro-apoptotic signalling upon toll-like receptor (TLR) stimulation in myeloid cells is normally antagonized by the simultaneous activation of anti-apoptotic pathways. We have previously reported that IFN-α can sensitize human monocytes to apoptosis induction by lipopolysaccharide (LPS). Based on these results we investigated whether similarly apoptosis can be cooperatively induced in myeloid tumor cells. When testing established acute myeloid leukemia (AML) cell lines we found the monocytic cell line THP-1 to be sensitive to IFN-α plus LPS induced apoptosis, which was partially dependent on caspase-8 and was associated with an enhanced expression of Fas/CD95. We extended our study to 29 short term blast lines from patients with AML and observed additive effects of IFN-α and LPS on cell death only with few samples indicating that sensitivity to IFN-α plus LPS inducible apoptosis is present in a fraction of AML samples only with no obvious correlation with certain FAB phenotypes.