{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T13:53:43Z","timestamp":1776347623249,"version":"3.51.2"},"reference-count":77,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jose Carreras Leukemia Stiftung (DJCLS)","award":["DJCLS 18R\/2022"],"award-info":[{"award-number":["DJCLS 18R\/2022"]}]},{"name":"Jose Carreras Leukemia Stiftung (DJCLS)","award":["70114844"],"award-info":[{"award-number":["70114844"]}]},{"name":"Deutsche Krebshilfe e.V.","award":["DJCLS 18R\/2022"],"award-info":[{"award-number":["DJCLS 18R\/2022"]}]},{"name":"Deutsche Krebshilfe e.V.","award":["70114844"],"award-info":[{"award-number":["70114844"]}]},{"name":"UMEA Clinician Scientist- Program of the medical faculty of the University of Duisburg Essen","award":["DJCLS 18R\/2022"],"award-info":[{"award-number":["DJCLS 18R\/2022"]}]},{"name":"UMEA Clinician Scientist- Program of the medical faculty of the University of Duisburg Essen","award":["70114844"],"award-info":[{"award-number":["70114844"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>WT1 is a true chameleon, both acting as an oncogene and tumor suppressor. As its exact role in leukemogenesis is still ambiguous, research with model systems representing natural conditions surrounding the genetic alterations in WT1 is necessary. In a cohort of 59 leukemia\/lymphoma cell lines, we showed aberrant expression for WT1 mRNA, which does not always translate into protein levels. We also analyzed the expression pattern of the four major WT1 protein isoforms in the cell lines and primary AML blasts with\/without WT1 mutations and demonstrated that the presence of mutations does not influence these patterns. By introduction of key intronic and exonic sequences of WT1 into a lentiviral expression vector, we developed a unique tool that can stably overexpress the four WT1 isoforms at their naturally occurring tissue-dependent ratio. To develop better cellular model systems for WT1, we sequenced large parts of its gene locus and also other important myeloid risk factor genes and revealed previously unknown alterations. Functionally, inhibition of the nonsense-mediated mRNA decay machinery revealed that under natural conditions, the mutated WT1 alleles go through a robust degradation. These results offer new insights and model systems regarding the characteristics of WT1 in leukemia and lymphoma.<\/jats:p>","DOI":"10.3390\/cancers15133491","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:37:28Z","timestamp":1688517448000},"page":"3491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Understanding WT1 Alterations and Expression Profiles in Hematological Malignancies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-4789","authenticated-orcid":false,"given":"Naghmeh","family":"Niktoreh","sequence":"first","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahshad","family":"Karimifard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6359-4035","authenticated-orcid":false,"given":"Lina Marie","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Breiter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aniththa","family":"Thivakaran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maren","family":"Soldierer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-6095","authenticated-orcid":false,"given":"Hans G\u00fcnther","family":"Drexler","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, Technical University of Braunschweig, 38106 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-4365","authenticated-orcid":false,"given":"Heiner","family":"Schaal","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital D\u00fcsseldorf, Medical Faculty, Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Sendker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-4483","authenticated-orcid":false,"given":"Dirk","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Hanenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Department of Otorhinolaryngology, Head & Neck Surgery, University Hospital D\u00fcsseldorf, Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrc3002","article-title":"Wilms\u2019 tumours: About tumour suppressor genes, an oncogene and a chameleon gene","volume":"11","author":"Huff","year":"2011","journal-title":"Nat. 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