{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:42:51Z","timestamp":1789382571176,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T00:00:00Z","timestamp":1390262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>T\u2010cell prolymphocytic leukemia (T\u2010PLL) is an aggressive post\u2010thymic T\u2010cell malignancy characterized by the recurrent inv(14)(q11q32)\/t(14;14)(q11;q32) or t(X;14)(q28;q11) leading to activation of either the <jats:italic>TCL1<\/jats:italic> or <jats:italic>MTCP1<\/jats:italic> gene, respectively. However, these primary genetic events are insufficient to drive leukemogenesis. Recently, activating mutations in <jats:italic>JAK3<\/jats:italic> have been identified in other T\u2010cell malignancies. Since JAK3 is essential for T\u2010cell maturation, we analyzed a cohort of 32 T\u2010PLL patients for mutational hot spots in the <jats:italic>JAK3<\/jats:italic> gene using a step\u2010wise screening approach. We identified 14 mutations in 11 of 32 patients (34%). The most frequently detected mutation in our cohort was M511I (seen in 57% of cases) previously described as an activating change in other T\u2010cell malignancies. Three patients carried two mutations in <jats:italic>JAK3<\/jats:italic>. In two patients M511I and R657Q were simultaneously detected and in another patient V674F and V678L. In the latter case we could demonstrate that the mutations were on the same allele in cis. Protein modeling and homology analyses of mutations present in other members of the JAK family suggested that these mutations likely activate JAK3, possibly by disrupting the activation loop and the interface between N and C lobes, increasing the accessibility of the catalytic loop. In addition, four of the 21 patients lacking a <jats:italic>JAK3<\/jats:italic> point mutation presented an aberrant karyotype involving the chromosomal band 19p13 harboring the <jats:italic>JAK3<\/jats:italic> locus. The finding of recurrent activating <jats:italic>JAK3<\/jats:italic> mutations in patients with T\u2010PLL could enable the use of JAK3 inhibitors to treat patients with this unfavorable malignancy who otherwise have a very poor prognosis. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22141","type":"journal-article","created":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T05:40:48Z","timestamp":1390282848000},"page":"309-316","source":"Crossref","is-referenced-by-count":81,"title":["Recurrent mutation of <i>JAK3<\/i> in T\u2010cell prolymphocytic leukemia"],"prefix":"10.1002","volume":"53","author":[{"given":"Anke K.","family":"Bergmann","sequence":"first","affiliation":[{"name":"Institute for Human Genetics Christian\u2010Albrechts\u2010University Kiel and University Hospital Schleswig\u2010Holstein Campus Kiel Kiel Germany"},{"name":"Department of Pediatrics Christian\u2010Albrechts\u2010University Kiel and University Hospital Schleswig\u2010Holstein Campus Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Schneppenheim","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics Christian\u2010Albrechts\u2010University Kiel and University Hospital Schleswig\u2010Holstein Campus Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Seifert","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research) Medical School Essen, University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Betts","sequence":"additional","affiliation":[{"name":"Cell Networks Excellenz Cluster Bioquant, University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Haake","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics Christian\u2010Albrechts\u2010University 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