{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:42:35Z","timestamp":1790901755206,"version":"4.1.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,11,10]]},"abstract":"<jats:p>\n                    HOX11, a divergent homeodomain-containing transcription factor, was isolated from the breakpoint of the nonrandom t(10;14)(q24;q11) chromosome translocation found in human T cell acute lymphoblastic leukemias. The translocation places the\n                    <jats:italic>HOX11<\/jats:italic>\n                    coding sequence under the transcriptional control of\n                    <jats:italic>TCR<\/jats:italic>\n                    \u03b1\/\u03b4 regulatory elements, resulting in ectopic expression of a normal HOX11 protein in thymocytes. To investigate the oncogenic potential of HOX11, we targeted its expression in lymphocytes of transgenic mice by placing the human cellular DNA under the transcriptional control of Ig heavy chain or LCK regulatory sequences. Only\n                    <jats:italic>IgH<\/jats:italic>\n                    <jats:sub>\u03bc<\/jats:sub>\n                    -\n                    <jats:italic>HOX11<\/jats:italic>\n                    mice expressing low levels of HOX11 were viable. During their second year of life, all\n                    <jats:italic>HOX11<\/jats:italic>\n                    transgenic mice became terminally ill with more than 75% developing large cell lymphomas in the spleen, which frequently disseminated to thymus, lymph nodes, and other nonhematopoietic tissues. Lymphoma cells were predominantly clonal IgM\n                    <jats:sup>+<\/jats:sup>\n                    IgD\n                    <jats:sup>+<\/jats:sup>\n                    mature B cells. Repopulation of severe combined immunodeficient mice with cells from hyperplastic spleens indicated that the\n                    <jats:italic>HOX11<\/jats:italic>\n                    tumor phenotype was transplantable. Before tumor development, expression of the transgene did not result in perturbations in lymphopoiesis; however, lymphoid hyperplasia involving the splenic marginal zones was present in 20% of spleens. Our studies provide direct evidence that expression of\n                    <jats:italic>HOX11<\/jats:italic>\n                    in lymphocytes leads to malignant transformation. These mice are a useful model system to study mechanisms involved in transformation from B-lineage hyperplasia to malignant lymphoma and for testing novel approaches to therapy. They represent a novel animal model for non-Hodgkin\u2019s lymphoma of peripheral mature B cell origin.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.23.13853","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"13853-13858","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["A model for spontaneous B-lineage lymphomas in\n                    <i>IgH<\/i>\n                    <sub>\u03bc<\/sub>\n                    <i>-HOX11<\/i>\n                    transgenic mice"],"prefix":"10.1073","volume":"95","author":[{"given":"Margaret R.","family":"Hough","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marciano D.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Singaraja","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn Marie","family":"Bryce","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Kamel-Reid","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving","family":"Dardick","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Breitman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sunnybrook Health Science Center, Toronto, Canada, M4N 3M5; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5G 1L5; Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5; Department of Pathology, The Toronto Hospital, Toronto, Canada, M5G 2C4; and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,11,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00227-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.004033"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/372143a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.4.1181.1181"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.11.2996.2996"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870020309"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.8.3161"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.20.8900"},{"key":"e_1_3_3_9_2","first-page":"226","volume":"54","author":"Kagan J","year":"1994","unstructured":"J Kagan, Y S Joe, E J Freireich Cancer Res 54, 226\u2013230 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1676542"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428199509049759"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90290-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.140281"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4431"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1634"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.11.1928"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.9.2909"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90016-Q"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(95)00364-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(95)00100-X"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90380-8"},{"key":"e_1_3_3_22_2","first-page":"1333","volume":"11","author":"Salvati P D","year":"1995","unstructured":"P D Salvati, P R Ranford, J Ford, U R Kees Oncogene 11, 1333\u20131338 (1995).","journal-title":"Oncogene"},{"key":"e_1_3_3_23_2","first-page":"1325","volume":"7","author":"Lu M","year":"1992","unstructured":"M Lu, N Zhang, A D Ho Oncogene 7, 1325\u20131330 (1992).","journal-title":"Oncogene"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/368747a0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90014-4"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/10.23.7731"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.8.2406"},{"key":"e_1_3_3_28_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. 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