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

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-alpha 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-alpha 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-alpha and LPS on cell death only with few samples indicating that sensitivity to IFN-alpha plus LPS inducible apoptosis is present in a fraction of AML samples only with no obvious correlation with certain FAB phenotypes.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Lehner M,Bailo M,Stachel D,Roesler W,Parolini O,Holter W

doi

10.1016/j.leukres.2007.05.001

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1729-35

issue

12

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(07)00181-6

journal_volume

31

pub_type

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