{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:44:23Z","timestamp":1792032263332,"version":"4.4.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,5,14]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>TCL1<\/jats:italic>\n                    gene at 14q32.1 is involved in chromosomal translocations and inversions in mature T cell leukemias. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectasia (AT) at a young age. In transgenic animals, the deregulated expression of\n                    <jats:italic>TCL1<\/jats:italic>\n                    leads to mature T cell leukemia, demonstrating the role of\n                    <jats:italic>TCL1<\/jats:italic>\n                    in the initiation of malignant transformation in T cell neoplasia. Expression of high levels of Tcl1 have also been found in a variety of human tumor-derived B cell lines ranging from pre-B cell to mature B cell. Here we describe the phenotype of transgenic mice, E\u03bc-\n                    <jats:italic>TCL1<\/jats:italic>\n                    , established with\n                    <jats:italic>TCL1<\/jats:italic>\n                    under the control of a V\n                    <jats:sub>H<\/jats:sub>\n                    promoter-Ig\n                    <jats:sub>H<\/jats:sub>\n                    -E\u03bc enhancer to target\n                    <jats:italic>TCL1<\/jats:italic>\n                    expression to immature and mature B cells. Flow cytometric analysis reveals a markedly expanded CD5\n                    <jats:sup>+<\/jats:sup>\n                    population in the peritoneal cavity of E\u03bc-\n                    <jats:italic>TCL1<\/jats:italic>\n                    mice starting at 2 mo of age that becomes evident in the spleen by 3\u20135 mo and in the bone marrow by 5\u20138 mo. Analysis of Ig gene rearrangements indicates monoclonality or oligoclonality in these populations, suggesting a preneoplastic expansion of CD5\n                    <jats:sup>+<\/jats:sup>\n                    B cell clones, with the elder mice eventually developing a chronic lymphocytic leukemia (CLL)-like disorder resembling human B-CLL. Our findings provide an animal model for CLL, the most common human leukemia, and demonstrate that deregulation of the Tcl1 pathway plays a crucial role in CLL pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.102181599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:46:49Z","timestamp":1027680409000},"page":"6955-6960","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":582,"title":["Human chronic lymphocytic leukemia modeled in mouse by targeted\n                    <i>TCL1<\/i>\n                    expression"],"prefix":"10.1073","volume":"99","author":[{"given":"Roberta","family":"Bichi","sequence":"first","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Shinton","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Martin","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoliy","family":"Koval","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Calin","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossano","family":"Cesari","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giandomenico","family":"Russo","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107; Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111; and Laboratory of Molecular Oncogenesis, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,5,14]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1308","volume-title":"Hematology: Basic Principles and Practice","author":"Rai K","year":"1995","unstructured":"K Rai, D C Patel Hematology: Basic Principles and Practice, eds R Hoffman, E J Banz, S J Shattil (Churchill Livingstone, New York), pp. 1308\u20131321 (1995)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.48.1.6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.155.2.623"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830081214"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(91)90136-H"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90552-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.24.7824"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6414084"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12530"},{"key":"e_1_3_3_10_2","first-page":"5452","volume":"57","author":"Narducci M G","year":"1997","unstructured":"M G Narducci, A Stoppacciaro, K Imada, T Uchiyama, L Virgilio, C Lazzeri, C M Croce, G Russo Cancer Res 57, 5452\u20135456 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_11_2","first-page":"379","volume":"12","author":"Thick J","year":"1996","unstructured":"J Thick, J A Metacalfe, Y-F Mak, D Beatty, Minegishi, M J S Dyer, G Lucas, A M R Taylor Oncogene 12, 379\u2013386 (1996).","journal-title":"Oncogene"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3885"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1998.tb03275.x"},{"key":"e_1_3_3_14_2","first-page":"2095","volume":"60","author":"Narducci M G","year":"2000","unstructured":"M G Narducci, E Pescarmona, C Lazzeri, S Signoretti, A M Lavinia, D Remotti, E Scala, C D Baroni, A Stoppacciaro, C M Croce, et al. 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