{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:24:58Z","timestamp":1790882698008,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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":[[2011,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Graft-versus-leukemia (GVL) against chronic-phase chronic myelogenous leukemia (CP-CML) is potent, but it is less efficacious against acute leukemias and blast-crisis chronic myelogenous leukemia (BC-CML). The mechanisms underlying GVL resistance are unknown. Previously, we found that alloreactive T cell targeting of GVL-sensitive bcr-abl\u2013induced mouse CP-CML (mCP-CML) required TCR\u2013MHC interactions and that multiple and redundant killing mechanisms were in play. To better understand why BC-CML is resistant to GVL, we performed a comprehensive analysis of GVL against mouse BC-CML (mBC-CML) induced by the retroviral transfer of the bcr-abl and NUP98\/HOXA9 fusion cDNAs. Like human BC-CML, mBC-CML was GVL resistant, and this was not due to accelerated kinetics or a greater leukemia burden. To study T cell recognition and killing mechanisms, we generated a panel of gene-deficient leukemias by transducing bone marrow from gene-deficient mice. T cell target recognition absolutely required that mBC-CML cells express MHC molecules. GVL against both mCP-CML and mBC-CML required leukemia expression of ICAM-1. We hypothesized that mBC-CML would be resistant to some of the killing mechanisms sufficient to eliminate mCP-CML, but we found instead that the same mechanisms were effective against both types of leukemia, because GVL was similar against wild-type or mBC-CML genetically lacking Fas, TRAIL-R, Fas\/TRAIL-R, or TNFR1\/R2 or when donor T cells were perforin\u2212\/\u2212. However, mCP-CML, but not mBC-CML, relied on expression of programmed death-1 ligands 1 and 2 (PD-L1\/L2) to resist T cell killing, because only GVL against mCP-CML was augmented when leukemias lacked PD-L1\/L2. Thus, mBC-CML cells have cell-intrinsic mechanisms, distinct from mCP-CML cells, which protect them from T cell killing.<\/jats:p>","DOI":"10.4049\/jimmunol.1100311","type":"journal-article","created":{"date-parts":[[2011,7,19]],"date-time":"2011-07-19T03:46:59Z","timestamp":1311047219000},"page":"1653-1663","source":"Crossref","is-referenced-by-count":30,"title":["Graft-versus-Leukemia (GVL) against Mouse Blast-Crisis Chronic Myelogenous Leukemia (BC-CML) and Chronic-Phase Chronic Myelogenous Leukemia (CP-CML): Shared Mechanisms of T Cell Killing, but Programmed Death Ligands Render CP-CML and Not BC-CML GVL Resistant"],"prefix":"10.1093","volume":"187","author":[{"given":"Catherine","family":"Matte-Martone","sequence":"first","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srividhya","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung Sheng","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Athanasiadis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Pavisic","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren D","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale Comprehensive Cancer Center, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,15]]},"reference":[{"key":"2025032410274373800_r1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nri775","article-title":"Cytolytic pathways in haematopoietic stem-cell transplantation","volume":"2","author":"van den Brink","year":"2002","journal-title":"Nat. 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