{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:08:50Z","timestamp":1792069730318,"version":"4.4.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"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":[[2019,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inhibitors of Bruton tyrosine kinase (BTK), a kinase downstream of BCR, display remarkable activity in a subset of mantle cell lymphoma (MCL) patients, but the drug resistance remains a considerable challenge. In this study, we demonstrate that aberrant expression of ROR1 (receptor tyrosine kinase-like orphan receptor 1), seen in a large subset of MCL, results in BCR\/BTK\u2013independent signaling and growth of MCL cells. ROR1 forms a functional complex with CD19 to persistently activate the key cell signaling pathways PI3K\u2013AKT and MEK\u2013ERK in the BCR\/BTK\u2013independent manner. This study demonstrates that ROR1\/CD19 complex effectively substitutes for BCR\u2013BTK signaling to promote activation and growth of MCL cells. Therefore, ROR1 expression and activation may represent a novel mechanism of resistance to inhibition of BCR\/BTK signaling in MCL. Our results provide a rationale to screen MCL patients for ROR1 expression and to consider new therapies targeting ROR1 and\/or CD19 or their downstream signaling pathways for MCL-expressing ROR1.<\/jats:p>","DOI":"10.4049\/jimmunol.1801327","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T19:15:13Z","timestamp":1568834113000},"page":"2043-2048","source":"Crossref","is-referenced-by-count":42,"title":["Cutting Edge: ROR1\/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor\u2013BTK Signaling Pathway"],"prefix":"10.1093","volume":"203","author":[{"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-7462","authenticated-orcid":false,"given":"Hong Y","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selene","family":"Nunez-Cruz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-4143","authenticated-orcid":false,"given":"Mowafaq","family":"Jillab","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Melnikov","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-5703","authenticated-orcid":false,"given":"Kavindra","family":"Nath","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Glickson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz A","family":"Wasik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Fox Chase Cancer Center , Philadelphia, PA 19111"},{"name":"Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"2025030417542973500_r1","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1200\/JCO.2015.63.5904","article-title":"Mantle cell lymphoma","volume":"34","author":"Cheah","year":"2016","journal-title":"J. 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