{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:56:07Z","timestamp":1791140167759,"version":"4.1.0"},"reference-count":39,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Translocations involving fibroblast growth factor receptor 3 (fgfr3) have been identified in about 25% of patients with myeloma. To directly examine the oncogenic potential offgfr3, murine bone marrow (BM) cells were transduced with retroviral vectors containing either wild-type fgfr3 or an activated mutant form of the receptor, fgfr3-TD. Mice transplanted with FGFR3-TD\u2013expressing BM developed a marked leukocytosis and lethal hematopoietic cell infiltration of multiple tissues within 6 weeks of transplantation. Secondary and tertiary recipients of spleen or BM from primary fgfr3-TD mice also developed tumors within 6 to 8 weeks. Analysis of the circulating tumor cells revealed a pre-B-cell phenotype in most mice, although immature T-lymphoid or mature myeloid populations also predominated in some animals. Enhanced lymphoid but not myeloid colony formation was observed in the early posttransplantation period and only interleukin 7 and FGF-responsive pre-B-cell lines could be established from tumors. Cell expansions in primary recipients appeared polyclonal, whereas tumors in later passages exhibited either clonal B- or T-cell receptor gene rearrangements. Mice transplanted with wild-type FGFR3-expressing BM developed delayed pro-B-cell lymphoma\/leukemias approximately 1 year after transplantation. These studies confirm that FGFR3 is transforming and can produce lymphoid malignancies in mice.<\/jats:p>","DOI":"10.1182\/blood.v97.8.2413","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"2413-2419","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":85,"title":["The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells"],"prefix":"10.1182","volume":"97","author":[{"given":"Zhihua","family":"Li","sequence":"first","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Plowright","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Leif","family":"Bergsagel","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Chesi","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Patterson","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa S.","family":"Hawley","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Hawley","sequence":"additional","affiliation":[{"name":"From the Departments of Medical Oncology and Pathology, The Princess Margaret Hospital, and The Toronto General Research Institute, ON; Weill Medical College, Cornell University, New York, NY; and Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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transcripts.","volume":"92","author":"Chesi","year":"1998","journal-title":"Blood."},{"key":"2020021218015551700_B6","first-page":"5640","article-title":"High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies.","volume":"58","author":"Avet-Loiseau","year":"1998","journal-title":"Cancer Res."},{"key":"2020021218015551700_B7","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1182\/blood.V91.12.4457","article-title":"Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma.","volume":"91","author":"Chesi","year":"1998","journal-title":"Blood."},{"key":"2020021218015551700_B8","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng1097-226","article-title":"Deregulation of MUM1\/IRF4 by chromosomal translocation in multiple myeloma.","volume":"17","author":"Iida","year":"1997","journal-title":"Nat Genet."},{"key":"2020021218015551700_B9","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1182\/blood.V90.2.526","article-title":"The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization.","volume":"90","author":"Nishida","year":"1997","journal-title":"Blood."},{"key":"2020021218015551700_B10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0092-8674(00)81069-7","article-title":"Fibroblast growth factor receptor 3 is a negative regulator of bone growth.","volume":"84","author":"Deng","year":"1996","journal-title":"Cell."},{"key":"2020021218015551700_B11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ng0496-390","article-title":"Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.","volume":"12","author":"Colvin","year":"1996","journal-title":"Nat Genet."},{"key":"2020021218015551700_B12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/ng0395-321","article-title":"Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.","volume":"9","author":"Tavormina","year":"1995","journal-title":"Nat Genet."},{"key":"2020021218015551700_B13","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1128\/MCB.16.8.4081","article-title":"Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II.","volume":"16","author":"Webster","year":"1996","journal-title":"Mol Cell Biol."},{"key":"2020021218015551700_B14","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1182\/blood.V95.3.992.003k29_992_998","article-title":"Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents 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production.","volume":"6","author":"Miller","year":"1986","journal-title":"Mol Cell Biol."},{"key":"2020021218015551700_B18","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0042-6822(88)90101-8","article-title":"Construction and use of a safe and efficient amphotropic packaging cell line.","volume":"167","author":"Markowitz","year":"1988","journal-title":"J Virol."},{"key":"2020021218015551700_B19","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1084\/jem.176.4.1149","article-title":"Transplantable myeloproliferative disease induced in mice by an interleukin 6 retrovirus.","volume":"176","author":"Hawley","year":"1992","journal-title":"J Exp Med."},{"key":"2020021218015551700_B20","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1084\/jem.178.4.1175","article-title":"Progenitor cell hyperplasia with rare development of myeloid leukemia in interleukin 11 bone marrow chimeras.","volume":"178","author":"Hawley","year":"1993","journal-title":"J Exp 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