{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:40:02Z","timestamp":1787510402449,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016669","name":"Sj\u00f6bergstiftelsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes & Cancer"],"published-print":{"date-parts":[[2023,10]]},"abstract":"Abstract<\/jats:title>\n \n Therapy\u2010resistant disease is a major cause of death in patients with acute lymphoblastic leukemia (ALL). Activation of the\n MYB<\/jats:italic>\n oncogene is associated with ALL and leads to uncontrolled neoplastic cell proliferation and blocked differentiation. Here, we used RNA\u2010seq to study the clinical significance of\n MYB<\/jats:italic>\n expression and\n MYB<\/jats:italic>\n alternative promoter (TSS2) usage in 133 pediatric ALLs. RNA\u2010seq revealed that all cases analyzed overexpressed\n MYB<\/jats:italic>\n and demonstrated\n MYB<\/jats:italic>\n TSS2 activity. qPCR analyses confirmed the expression of the alternative\n MYB<\/jats:italic>\n promoter also in seven ALL cell lines. Notably, high\n MYB<\/jats:italic>\n TSS2 activity was significantly associated with relapse (\n p<\/jats:italic>\n \u2009=\u20090.007). Moreover, cases with high\n MYB<\/jats:italic>\n TSS2 usage showed evidence of therapy\u2010resistant disease with increased expression of ABC multidrug resistance transporter genes (e.g.,\n ABCA2, ABCB5<\/jats:italic>\n , and\n ABCC10<\/jats:italic>\n ) and enzymes catalyzing drug degradation (e.g.,\n CYP1A2<\/jats:italic>\n ,\n CYP2C9<\/jats:italic>\n , and\n CYP3A5<\/jats:italic>\n ). Elevated\n MYB<\/jats:italic>\n TSS2 activity was further associated with augmented KRAS signaling (\n p<\/jats:italic>\n \u2009<\u20090.05) and decreased methylation of the conventional\n MYB<\/jats:italic>\n promoter (\n p<\/jats:italic>\n \u2009<\u20090.01). Taken together, our results suggest that\n MYB<\/jats:italic>\n alternative promoter usage is a novel potential prognostic biomarker for relapse and therapy resistance in pediatric ALL.\n <\/jats:p>","DOI":"10.1002\/gcc.23151","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T06:35:37Z","timestamp":1684823737000},"page":"597-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased\n \n MYB<\/i>\n <\/scp>\n alternative promoter usage is associated with relapse in acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-1392","authenticated-orcid":false,"given":"Andr\u00e9","family":"Fehr","sequence":"first","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Pathology University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Arvidsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Nordlund","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudmar","family":"L\u00f6nnerholm","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-7363","authenticated-orcid":false,"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Pathology University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-2048","authenticated-orcid":false,"given":"Mattias K.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Pathology University of Gothenburg Gothenburg 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