{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T10:21:16Z","timestamp":1765534876864,"version":"3.48.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2021.21"],"award-info":[{"award-number":["DKS 2021.21"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Paediatric blast\u2010phase chronic myeloid leukaemia (CML\u2010BP) is a rare and serious condition. Of 231 paediatric patients enrolled in the German CML\u2010PAED\u2010II registry between January 2007 and September 2023, 25 individuals (11%) were diagnosed with CML\u2010BP. To identify genetic variants associated with early onset and disease transformation, we performed whole genome sequencing (WGS), deep targeted sequencing and cytogenetic analyses in 19 cases with de novo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911) or secondary (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) CML\u2010BP and sufficient available biomaterial. Copy number variants (CNVs) were more frequent than single nucleotide variants (SNVs) and more prevalent in secondary than in de novo CML\u2010BP. Recurrent pathogenic somatic SNVs were observed in\n                    <jats:italic>ABL1<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095, 24%),\n                    <jats:italic>RUNX1<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092, 12%) and\n                    <jats:italic>ASXL1<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092, 12%). Nine patients (47%) carried pathogenic germline (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) or somatic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091) variants in either of the genes\n                    <jats:italic>ATM<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>FANCM<\/jats:italic>\n                    ,\n                    <jats:italic>HERC2<\/jats:italic>\n                    ,\n                    <jats:italic>NBN<\/jats:italic>\n                    ,\n                    <jats:italic>RAD54B<\/jats:italic>\n                    ,\n                    <jats:italic>RECQL4<\/jats:italic>\n                    ,\n                    <jats:italic>SETD2<\/jats:italic>\n                    or\n                    <jats:italic>TP63<\/jats:italic>\n                    belonging to the DNA damage response (DDR). Within a comparison cohort of 19 patients with chronic phase paediatric CML, only one individual (5%) exhibited a pathogenic DDR germline variant. Our study provides novel pathogenetic insights into paediatric CML\u2010BP. The identification of pathogenic DDR\u2010associated germline variants suggests a genetic predisposition with potential implications for patients and families concerning cancer treatment and surveillance.\n                  <\/jats:p>","DOI":"10.1111\/bjh.20133","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:15:02Z","timestamp":1746749702000},"page":"141-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic variant profiling in blast\u2010phase paediatric chronic myeloid leukaemia: Predisposing and driving alterations"],"prefix":"10.1111","volume":"207","author":[{"given":"Yvonne Lisa","family":"Behrens","sequence":"first","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"},{"name":"Institute of Medical Genetics Carl von Ossietzky University Oldenburg  Oldenburg 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