{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T14:01:41Z","timestamp":1768831301614,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"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":[[2012,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Transient myeloproliferative disorder (<jats:styled-content style=\"fixed-case\">TMD<\/jats:styled-content>) of the newborn and acute megakaryoblastic leukaemia (<jats:styled-content style=\"fixed-case\">AMKL<\/jats:styled-content>) in children with Down syndrome (<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010chromosomal transcription factor <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1 synergize to trigger <jats:styled-content style=\"fixed-case\">TMD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AMKL<\/jats:styled-content> in most patients. Here, we report the occurrence of <jats:styled-content style=\"fixed-case\">TMD<\/jats:styled-content>, which spontaneously remitted and later progressed to <jats:styled-content style=\"fixed-case\">AMKL<\/jats:styled-content> in a patient without <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> but with a distinct dysmorphic syndrome. Genetic analysis of the leukaemic clone revealed somatic trisomy 21 and a truncating <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1<\/jats:italic> mutation. The analysis of the patient's normal blood cell <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> on a genomic single nucleotide polymorphism (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>) array revealed a <jats:italic>de novo<\/jats:italic> germ line 2\u00b758\u00a0<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>b 15q24 microdeletion including 41 known genes encompassing the tumour suppressor <jats:italic><jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content><\/jats:italic>. Genomic context analysis of proteins encoded by genes that are included in the microdeletion, chromosome 21\u2010encoded proteins and <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1 suggests that the microdeletion may trigger leukaemogenesis by disturbing the balance of a hypothetical regulatory network of normal megakaryopoiesis involving <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> SUMO<\/jats:styled-content>3 and <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>1. The 15q24 microdeletion may thus represent the first genetic hit to initiate leukaemogenesis and implicates <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SUMO<\/jats:styled-content>3 as novel components of the leukaemogenic network in <jats:styled-content style=\"fixed-case\">TMD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AMKL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09028.x","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T10:08:54Z","timestamp":1328090934000},"page":"180-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A 15q24 microdeletion in transient myeloproliferative disease (<scp>TMD<\/scp>) and acute megakaryoblastic leukaemia (<scp>AMKL<\/scp>) implicates <scp>PML<\/scp> and <scp>SUMO<\/scp>3 in the leukaemogenesis of <scp>TMD<\/scp>\/<scp>AMKL<\/scp>"],"prefix":"10.1111","volume":"157","author":[{"given":"Susanne","family":"Haemmerling","sequence":"first","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology University of Heidelberg Medical Centre Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Behnisch","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Haematology and Immunology University of Heidelberg Medical Centre Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Doerks","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan O.","family":"Korbel","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peer","family":"Bork","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Moog","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Heidelberg Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Hentze","sequence":"additional","affiliation":[{"name":"Endocrinology and Human Genetics Laboratory and Consultation Centre Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Grasshoff","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Tuebingen Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bonin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Tuebingen Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Rie\u00df","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Tuebingen Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes W. 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