{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:53:31Z","timestamp":1773287611865,"version":"3.50.1"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Treatment of hematopoietic malignancies often requires allogeneic bone marrow transplantation, and the subsequent graft-versus-leukemia response is crucial for the elimination of malignant cells. Cytotoxic T lymphocytes and NK cells responsible for the immunoelimination express Fas ligand and strongly rely on the induction of Fas receptor-mediated apoptosis for their action. Although cancer cells are removed successfully by graft-versus-leukemia reactions in myeloid malignancies, their efficiency is low in T cell leukemias. This may be partially because of the ability of malignant T cells to escape apoptosis. Our work shows that Eph family receptor EphB3 is consistently expressed by malignant T lymphocytes, most frequently in combination with EphB6, and that stimulation with their common ligands, ephrin-B1 and ephrin-B2, strongly suppresses Fas-induced apoptosis in these cells. This effect is associated with Akt activation and with the inhibition of the Fas receptor-initiated caspase proteolytic cascade. Akt proved to be crucial for the prosurvival response, because inhibition of Akt, but not of other molecules central to T cell biology, including Src kinases, MEK1 and MEK2, blocked the antiapoptotic effect. Overall, this demonstrates a new role for EphB receptors in the protection of malignant T cells from Fas-induced apoptosis through Akt engagement and prevention of caspase activation. Because Fas-triggered apoptosis is actively involved in the graft-versus-leukemia response and cytotoxic T cells express ephrin-Bs, our observations suggest that EphB receptors are likely to support immunoevasivenes of T cell malignancies and may represent promising targets for therapies, aiming to enhance immunoelimination of cancerous T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1003482","type":"journal-article","created":{"date-parts":[[2011,10,29]],"date-time":"2011-10-29T03:46:49Z","timestamp":1319860009000},"page":"5983-5994","source":"Crossref","is-referenced-by-count":35,"title":["EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes"],"prefix":"10.1093","volume":"187","author":[{"given":"Alison","family":"Maddigan","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Regina , Regina, Saskatchewan S4S 0A2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Truitt","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Arsenault","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Freywald","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odette","family":"Allonby","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Regina , Regina, Saskatchewan S4S 0A2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aru","family":"Narendran","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Alberta Children\u2019s Hospital , Calgary, Alberta T2N 4N2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Xiang","sequence":"additional","affiliation":[{"name":"Saskatoon Cancer Center, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Weng","sequence":"additional","affiliation":[{"name":"Terry Fox Laboratory, British Columbia Cancer Agency , Vancouver, British Columbia V5Z 1L3 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Napper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Freywald","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan S7N 0W8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,12,1]]},"reference":[{"key":"2025032410501265100_r1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-2141.2008.07314.x","article-title":"Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia","volume":"143","author":"Van Vlierberghe","year":"2008","journal-title":"Br. 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