{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:40:53Z","timestamp":1781109653790,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,10,10]]},"abstract":"<jats:p>CD19 receptor is expressed at high levels on human B-lineage lymphoid cells and is physically associated with the Src protooncogene family protein-tyrosine kinase Lyn. Recent studies indicate that the membrane-associated CD19-Lyn receptor-enzyme complex plays a pivotal role for survival and clonogenicity of immature B-cell precursors from acute lymphoblastic leukemia patients, but its significance for mature B-lineage lymphoid cells (e.g., B-lineage lymphoma cells) is unknown. CD19-associated Lyn kinase can be selectively targeted and inhibited with B43-Gen, a CD19 receptor-specific immunoconjugate containing the naturally occurring protein-tyrosine kinase inhibitor genistein (Gen). We now present experimental evidence that targeting the membrane-associated CD19-Lyn complex in vitro with B43-Gen triggers rapid apoptotic cell death in highly radiation-resistant p53-Bax- Ramos-BT B-lineage lymphoma cells expressing high levels of Bcl-2 protein without affecting the Bcl-2 expression level. The therapeutic potential of this membrane-directed apoptosis induction strategy was examined in a scid mouse xenograft model of radiation-resistant high-grade human B-lineage lymphoma. Remarkably, in vivo treatment of scid mice challenged with an invariably fatal number of Ramos-BT cells with B43-Gen at a dose level &lt; 1\/10 the maximum tolerated dose resulted in 70% long-term event-free survival. Taken together, these results provide unprecedented evidence that the membrane-associated anti-apoptotic CD19-Lyn complex may be at least as important as Bcl-2\/Bax ratio for survival of lymphoma cells.<\/jats:p>","DOI":"10.1073\/pnas.92.21.9575","type":"journal-article","created":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T20:53:44Z","timestamp":1149195224000},"page":"9575-9579","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells."],"prefix":"10.1073","volume":"92","author":[{"given":"D E","family":"Myers","sequence":"first","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Jun","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K G","family":"Waddick","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Forsyth","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Chelstrom","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R L","family":"Gunther","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N E","family":"Tumer","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bolen","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F M","family":"Uckun","sequence":"additional","affiliation":[{"name":"Biotherapy Program, University of Minnesota Health Sciences Center, Minneapolis 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,10,10]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.21.9575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:03:40Z","timestamp":1649858620000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.21.9575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,10,10]]},"references-count":0,"journal-issue":{"issue":"21","published-print":{"date-parts":[[1995,10,10]]}},"alternative-id":["10.1073\/pnas.92.21.9575"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.21.9575","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,10,10]]},"assertion":[{"value":"1995-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}