Fas/APO-1 Expression and Function on Malignant Cells of Hematologic and Nonhematologic Origin

Owen‐Schaub, Laurie B.; Meterissian, Sarki; Ford, R.

doi:10.1097/00002371-199310000-00011

Cited by 75 publications

(34 citation statements)

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“…Our finding that CD95 is expressed constitutively, albeit often weakly, in the majority of primary B-lineage leukaemias is in line with recent studies employing sensitive methods for the detection of CD95 expression (Owen-Schaub et al, 1993;Karawajew et al, 1997). We have confirmed that, despite expressing CD95, most of these leukaemias are resistant toward CD95-mediated apoptosis (Owen-Schaub et al, 1993;Karawajew et al, 1997).…”

Section: Discussionsupporting

confidence: 90%

Mutation analysis of CD95 (APO‐1/Fas) in childhood B‐lineage acute lymphoblastic leukaemia

et al. 1998

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Summary. The CD95 system plays an important role in lymphocyte homeostasis, has been implicated in the development of lymphoid malignancies, exerts a tumour suppressor function, and contributes to drug-induced cytotoxicity. We hypothesized that mutations of CD95 may occur in childhood B-lineage acute lymphoblastic leukaemia (ALL), a disease known for its constitutive resistance towards CD95-mediated apoptosis. We investigated 32 primary Blineage ALL of childhood and five B-lineage ALL cell lines. All primary leukaemias expressed CD95 and bcl-2 to a variable degree. Most of the leukaemias were resistant towards CD95-mediated apoptosis. However, using SSCP analysis, no mutations in the coding and proximal promoter region could be detected. We conclude that the resistance towards CD95-mediated apoptosis observed in most de novo Blineage ALL is not caused by mutations of the CD95 death receptor.Keywords: CD95 (APO-1/Fas), apoptosis, B-lineage acute lymphoblastic leukaemia, mutation.The APO-1 (CD95/Fas) system is pivotal in maintaining both B-and T-cell equilibrium and plays an important role in growth control of other cell types (reviewed by Nagata, 1997). Many cell types, both normal and malignant, express CD95 including cells of B-lineage (Leithäuser et

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Section: Discussionsupporting

confidence: 90%

Mutation analysis of CD95 (APO‐1/Fas) in childhood B‐lineage acute lymphoblastic leukaemia

et al. 1998

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“…Third, although the major role of the Fas pathway is to induce apoptosis on engagement of FasL with the Fas receptor, it has also been demonstrated that Fas signaling can result in proliferation, depending on the type of cell and the environmental conditions (48 -50). In tumors of hematologic and nonhematologic origin, treatment with anti-Fas Ab can promote cell growth instead of apoptosis (51). We have shown previously that FADD protein expression is lost during the development of thyroid adenoma and adenocarcinoma and that agonistic anti-Fas Ab accelerates Fas ϩ FADD Ϫ thyroid follicular cell growth in vitro (34).…”

Section: Discussionmentioning

confidence: 98%

Absence or Low Expression of Fas-Associated Protein with Death Domain in Acute Myeloid Leukemia Cells Predicts Resistance to Chemotherapy and Poor Outcome

et al. 2004

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04). In multivariate analysis, FADD؊/low protein expression was independently associated with a poor EFS and overall survival (P ‫؍‬ 0.002 and P ‫؍‬ 0.026, respectively). Importantly, FADD ؊/low protein expression predicted poor EFS even in patients with standard-or good-risk AML (P ‫؍‬ 0.009). Thus, we identified low or absent expression of the FADD protein in leukemic cells at diagnosis as a poor independent prognostic factor that can predict worse clinical outcome even for patients with standard-or good-risk AML.

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“…This study shows that malignant glioma cells express The cytokines were added to the cultures for 24 h in DME/10% FCS at the concentrations indicated. The cells were washed and then exposed to Fas ab (1 ,ug/ml; 0.1 og/ml for LN-18) in DME/0.5% FCS for 24 (10,36,46). Induction of Fas/APO-l cell surface expression by IFNy and TNFa has been described (10,19,37,47).…”

Section: Discussionmentioning

confidence: 99%

Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines.

Weller¹,

Frei²,

Groscurth³

et al. 1994

J. Clin. Invest.

337

288

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Fas/APO-1 is a transmembrane protein of the nerve growth factor/TNFa receptor family which signals apoptotic cell death in susceptible target cells. We have investigated the susceptibility of seven human malignant glioma cell lines to Fas/APO-1-dependent apoptosis. Sensitivity to Fas/APO-1 antibody-mediated cell killing correlated with cell surface expression of Fas/APO-1. Expression of Fas/APO-1 as well as Fas/APO-1-dependent cytotoxicity were augmented by preexposure of human malignant glioma cells to IFNy and TNFa. Further, pretreatment with TGFp2, IL1 and IL8 enhanced Fas/APO-1 antibody-induced glioma cell apoptosis whereas other cytokines including TNFfi, IL6, macrophage colony-stimulating factor, IL10 and EL13 had no such effect. None of the human malignant glioma cell lines was susceptible to TNFa-induced cytotoxicity. Fas/ APO-1 antibody-sensitive glioma cell lines (n = 5), but not Fas/APO-1 antibody-resistant glioma cell lines (n = 2), became sensitive to TNFa when co-treated with inhibitors of RNA and protein synthesis. Resistance of human glioma cells to Fas/APO-1 antibody-mediated apoptosis was mainly related to low level expression of Fas/APO-1 and appeared not to be linked to overexpression of the antiapoptotic protooncogene, bcl-2. Given the resistance of human malignant glioma to surgery, irradiation, chemotherapy and immunotherapy, we propose that Fas/APO-1 may be a promising target for a novel locoregionary approach to human malignant glioma. This strategy gains support from the demonstration of Fas/APO-1 expression in ex vivo human malignant glioma specimens and from the absence of Fas/APO-1 in normal human brain parenchyma. (J. Clin. Invest. 1994. 94:954-964.)

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Fas/APO-1 Expression and Function on Malignant Cells of Hematologic and Nonhematologic Origin

Cited by 75 publications

References 0 publications

Mutation analysis of CD95 (APO‐1/Fas) in childhood B‐lineage acute lymphoblastic leukaemia

Mutation analysis of CD95 (APO‐1/Fas) in childhood B‐lineage acute lymphoblastic leukaemia

Absence or Low Expression of Fas-Associated Protein with Death Domain in Acute Myeloid Leukemia Cells Predicts Resistance to Chemotherapy and Poor Outcome

Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines.

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