{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:14:41Z","timestamp":1777054481426,"version":"3.51.4"},"reference-count":48,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although hairy cell leukemia is uniquely sensitive to interferon-\u03b1 (IFN-\u03b1), the biologic basis for this phenomenon remains unclear. Here we examine the effects of IFN-\u03b1 on cultured hairy cells (HCs), taking into account the possible modifying influence of cell adhesion. We make the novel observation that therapeutic concentrations of IFN-\u03b1 kill nonadherent HCs by inducing apoptosis. In keeping with the persistence of HCs in tissues during therapy, such killing was inhibited by integrin-mediated adhesion to vitronectin or fibronectin. Exposure of HCs to IFN-\u03b1 resulted in a marked increase in tumor necrosis factor-\u03b1 (TNF-\u03b1) secretion. Furthermore, blocking antibodies to TNF-RI or TNF-RII protected HCs from IFN-\u03b1\u2013induced apoptosis, demonstrating that such killing was mediated by TNF-\u03b1. In the absence of IFN-\u03b1, exogenous TNF-\u03b1 did not induce HC apoptosis, showing that IFN-\u03b1 sensitized HCs to the proapoptotic effect of autocrine TNF-\u03b1. This sensitization to TNF-\u03b1\u2013induced killing was attributable to suppression of IAP (inhibitors of apoptosis) production known to be regulated by the cytoprotective nuclear factor\u2013\u03baB\u2013dependent arm of TNF-\u03b1 signaling. Moreover, engagement of the receptors for fibronectin or vitronectin prevented this IFN-\u03b1\u2013induced down-regulation of IAPs. Understanding of the signals involved in the combined effects of IFN-\u03b1 and TNF-\u03b1 and abrogation of those induced by integrin engagement offers the possibility of sensitizing other malignant cells to IFN-\u03b1\u2013induced killing and thereby extending the therapeutic use of this cytokine.<\/jats:p>","DOI":"10.1182\/blood.v100.2.647","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T21:48:18Z","timestamp":1033508898000},"page":"647-653","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":50,"title":["Response of hairy cells to IFN-\u03b1 involves induction of apoptosis through autocrine TNF-\u03b1 and protection by adhesion"],"prefix":"10.1182","volume":"100","author":[{"given":"Peter K.","family":"Baker","sequence":"first","affiliation":[{"name":"From the Department of Haematology, University of Liverpool, United 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