{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:04:38Z","timestamp":1792267478760,"version":"4.4.0"},"reference-count":22,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Notch receptors mediate cell-fate decisions through interaction with specific ligands during development. The biological role of a novel Notch ligand, Dll4, in mice was explored by reconstituting lethally irradiated mice with bone marrow (BM) cells transduced with Dll4 retroviral vector. White blood cell and lymphocyte counts in Dll4-overexpressing mice were reduced at the early stage of reconstitution but increased significantly at approximately 10 weeks after BM transplantation. BM, spleen, lymph nodes, and peripheral blood ofDll4-overexpressing mice contained predominantly CD4+CD8+ T cells and virtually lacked B cells. The Dll4-overexpressing mice eventually developed a lethal phenotype that was characterized by the progression of a T-cell lymphoproliferative disease (restricted to BM and lymphoid tissues) to transplantable monoclonal T-cell leukemia\/lymphoma scattered to multiple organs. Results suggest that the interaction of Dll4with Notch1 may provide key signals for T-cell development.<\/jats:p>","DOI":"10.1182\/blood.v98.13.3793","type":"journal-article","created":{"date-parts":[[2002,10,28]],"date-time":"2002-10-28T20:44:12Z","timestamp":1035837852000},"page":"3793-3799","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":80,"title":["A novel Notch ligand, Dll4, induces T-cell leukemia\/lymphoma when overexpressed in mice by retroviral-mediated gene transfer"],"prefix":"10.1182","volume":"98","author":[{"given":"Xiao-Qiang","family":"Yan","sequence":"first","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Sarmiento","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Guo","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Juan","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwyneth","family":"Van","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ying","family":"Qi","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Scully","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Senaldi","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"From the Department of Pathology\/Pharmacology, Amgen, Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217094366900_B1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1126\/science.284.5415.770","article-title":"Notch signaling: cell fate control and signal integration in development.","volume":"284","author":"Artavanis","year":"1999","journal-title":"Science."},{"key":"2020021217094366900_B2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/0092-8674(91)90111-B","article-title":"TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.","volume":"66","author":"Ellisen","year":"1991","journal-title":"Cell."},{"key":"2020021217094366900_B3","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1084\/jem.183.5.2283","article-title":"Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles.","volume":"183","author":"Pear","year":"1996","journal-title":"J Exp Med."},{"key":"2020021217094366900_B4","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1038\/sj.onc.1201035","article-title":"The mouse mammary tumor associated gene Int3 is a unique member of the Notch gene family (Notch4).","volume":"14","author":"Gallahan","year":"1997","journal-title":"Oncogene."},{"key":"2020021217094366900_B5","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1242\/dev.122.7.2251","article-title":"Notch4\/int-3, a mammary proto-oncogene, is anendothelial cell-specific mammalian Notch gene.","volume":"122","author":"Uyttendaele","year":"1996","journal-title":"Development."},{"key":"2020021217094366900_B6","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1101\/gad.6.3.345","article-title":"Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.","volume":"6","author":"Jhappan","year":"1992","journal-title":"Genes Dev."},{"key":"2020021217094366900_B7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0925-4773(96)00589-8","article-title":"Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development.","volume":"59","author":"Lardelli","year":"1996","journal-title":"Mech Dev."},{"key":"2020021217094366900_B8","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.1128\/JVI.70.11.8071-8080.1996","article-title":"Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma.","volume":"70","author":"Rohn","year":"1996","journal-title":"J Virol."},{"key":"2020021217094366900_B9","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1101\/gad.14.11.1313","article-title":"Dll4, a novel Notch ligand expressed in arterial endothelium.","volume":"14","author":"Shutter","year":"2000","journal-title":"Genes Dev."},{"key":"2020021217094366900_B10","first-page":"136","article-title":"Versatile retroviral vectors for potential use in gene therapy.","volume":"1","author":"Hawley","year":"1994","journal-title":"Gene Ther."},{"key":"2020021217094366900_B11","doi-asserted-by":"crossref","first-page":"8392","DOI":"10.1073\/pnas.90.18.8392","article-title":"Production of high-titer helper-free retroviruses by transient transfection.","volume":"90","author":"Pear","year":"1993","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021217094366900_B12","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1182\/blood.V86.11.4025.bloodjournal86114025","article-title":"Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice.","volume":"86","author":"Yan","year":"1995","journal-title":"Blood."},{"key":"2020021217094366900_B13","volume-title":"Molecular Cloning.","author":"Sambrook","year":"1989"},{"key":"2020021217094366900_B14","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/intimm\/11.7.1017","article-title":"Expression pattern of notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development.","volume":"11","author":"Felli","year":"1999","journal-title":"Int Immunol."},{"key":"2020021217094366900_B15","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S1074-7613(00)80105-3","article-title":"Notch1 expression in early lymphopoiesis influences B versus T lineage determination.","volume":"11","author":"Pui","year":"1999","journal-title":"Immunity."},{"key":"2020021217094366900_B16","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1182\/blood.V91.11.4084","article-title":"The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells.","volume":"91","author":"Varnum","year":"1998","journal-title":"Blood."},{"key":"2020021217094366900_B17","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0301-472X(00)00146-6","article-title":"Expression of notch receptors, notch ligands, and fringe genes in hematopoiesis.","volume":"28","author":"Singh","year":"2000","journal-title":"Exp Hematol."},{"key":"2020021217094366900_B18","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1182\/blood.V83.8.2057.2057","article-title":"A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.","volume":"83","author":"Milner","year":"1994","journal-title":"Blood."},{"key":"2020021217094366900_B19","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1182\/blood.V95.9.2847.009k19_2847_2854","article-title":"Monocytes express high amounts of Notch and undergo cytokine specific apoptosis following interaction with the Notch ligand, Delta-1.","volume":"95","author":"Ohishi","year":"2000","journal-title":"Blood."},{"key":"2020021217094366900_B20","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0092-8674(00)81368-9","article-title":"An activated form of Notch influences the choice between CD4 and CD8 T cell lineages.","volume":"87","author":"Robey","year":"1996","journal-title":"Cell."},{"key":"2020021217094366900_B21","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0092-8674(00)81929-7","article-title":"Notch activity influences the alphabeta versus gammadelta T cell lineage decision.","volume":"88","author":"Washburn","year":"1997","journal-title":"Cell."},{"key":"2020021217094366900_B22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1074-7613(00)80054-0","article-title":"Deficient T cell fate specification in mice with an induced inactivation of Notch1.","volume":"10","author":"Radtke","year":"1999","journal-title":"Immunity."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/98\/13\/3793\/1679188\/h8240103793.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/98\/13\/3793\/1679188\/h8240103793.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T20:10:41Z","timestamp":1682280641000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/98\/13\/3793\/90243\/A-novel-Notch-ligand-Dll4-induces-Tcell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,15]]},"references-count":22,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2001,12,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v98.13.3793","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,12,15]]}}}