{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:15:11Z","timestamp":1790752511373,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The development of hematopoietic neoplasms is often associated with mutations, altered gene expression or chromosomal translocations. Recently, the t(5, 9)(q33;q22) translocation was found in a subset of peripheral T cell lymphomas and was shown to result in an IL-2\u2013inducible kinase\u2013spleen tyrosine kinase (ITK-Syk) fusion transcript. In this study, we show that T cell\u2013specific expression of the ITK-Syk oncogene in mice leads to an early onset and aggressive polyclonal T cell lymphoproliferation with concomitant B cell expansion and systemic inflammation by 7\u20139 wk of age. Because this phenotype is strikingly different from previous work showing that ITK-Syk expression causes clonal T cell lymphoma by 20\u201327 wk of age, we investigated the underlying molecular mechanism in more detail. We show that the reason for the severe phenotype is the lack of B-lymphocyte\u2013induced maturation protein-1 (Blimp-1) induction by low ITK-Syk expression. In contrast, high ITK-Syk oncogene expression induces terminal T cell differentiation in the thymus by activating Blimp-1, thereby leading to elimination of oncogene-expressing cells early in development. Our data suggest that terminal differentiation is an important mechanism to prevent oncogene-expressing cells from malignant transformation, as high ITK-Syk oncogene activity induces cell elimination. Accordingly, for transformation, a specific amount of oncogene is required, or alternatively, the induction of terminal differentiation is defective.<\/jats:p>","DOI":"10.4049\/jimmunol.1300420","type":"journal-article","created":{"date-parts":[[2013,12,28]],"date-time":"2013-12-28T03:47:11Z","timestamp":1388202431000},"page":"1024-1033","source":"Crossref","is-referenced-by-count":13,"title":["Premature Terminal Differentiation Protects from Deregulated Lymphocyte Activation by ITK-Syk"],"prefix":"10.1093","volume":"192","author":[{"given":"Martina P","family":"Bach","sequence":"first","affiliation":[{"name":"Institute of Immunology, University Clinics Ulm , 89081 Ulm,","place":["Germany"]},{"name":"Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max Planck Institute of Immunobiology and Epigenetics , 79108 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hug","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max Planck Institute of Immunobiology and Epigenetics , 79108 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Werner","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Clinics Ulm , 89081 Ulm,","place":["Germany"]},{"name":"Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max Planck Institute of Immunobiology and Epigenetics , 79108 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Holch","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , 81675 Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Sprissler","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, University Medical Center Freiburg , 79106 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"Pechloff","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , 81675 Munich,","place":["Germany"]},{"name":"German Cancer Consortium, German Cancer Research Center , 69120 Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Zirlik","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, University Medical Center Freiburg , 79106 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, University Medical Center Freiburg , 79106 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Dierks","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, University Medical Center Freiburg , 79106 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Ruland","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen , 81675 Munich,","place":["Germany"]},{"name":"German Cancer Consortium, German Cancer Research Center , 69120 Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Jumaa","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Clinics Ulm , 89081 Ulm,","place":["Germany"]},{"name":"Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg and Max Planck Institute of Immunobiology and Epigenetics , 79108 Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,1]]},"reference":[{"key":"2025032404104697200_r1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/oxfordjournals.jbchem.a002970","article-title":"Structure and function of Syk protein-tyrosine kinase","volume":"130","author":"Sada","year":"2001","journal-title":"J. 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