{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:51:05Z","timestamp":1790988665118,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T00:00:00Z","timestamp":1351555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>), <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic> mutation and deletion are strongly associated with one another and with adverse clinical outcome. Mutant <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53 protein typically accumulates to high levels and has been reported to have transcriptional regulatory activity distinct from that of wild\u2010type <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53. To investigate whether such an effect is relevant to <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>, carefully balanced primary <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> samples with or without <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic> mutation\/deletion were compared for their gene expression profiles using high\u2010density <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> microarrays. Ninety\u2010six and eight differentially expressed genes were identified, respectively, using two alternative statistical approaches with different stringencies. None of the differentially expressed genes were known to be regulated by mutant <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53, and only four of the 67 under\u2010expressed genes were known transcriptional targets of wild\u2010type <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53. Significantly, both approaches showed that gene under\u2010expression was the dominant feature of <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic>\u2010mutant <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> samples. Furthermore, a disproportionate number of the under\u2010expressed genes were located on chromosome 17p, the most significant being <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic> itself. Together, these results indicate that any transcriptional regulatory effects of mutant <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53 in <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cells are overshadowed by the under\u2010expression of co\u2010deleted <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic> and other genes on chromosome 17p. Our findings have implications for emerging therapeutic strategies that target mutant <jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53.<\/jats:p>","DOI":"10.1111\/bjh.12092","type":"journal-article","created":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T11:41:35Z","timestamp":1351597295000},"page":"53-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The gene expression signature associated with <i><scp>TP<\/scp>53<\/i> mutation\/deletion in chronic lymphocytic leukaemia is dominated by the under\u2010expression of <i><scp>TP<\/scp>53<\/i> and other genes on chromosome 17p"],"prefix":"10.1111","volume":"160","author":[{"given":"Ke","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool UK"},{"name":"Department of Haematology Royal Liverpool and Broadgreen University Hospitals NHS Trust Liverpool 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