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To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T\u2010ALL patients were characterized by genome\u2010wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.015) and older epigenetic (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and mitotic age (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely <jats:italic>TLX3, HOXA9, HOXA10,<\/jats:italic> and <jats:italic>NKX2\u20101<\/jats:italic>, and novel genes in T\u2010ALL biology including <jats:italic>PLCB4, PLXND1<\/jats:italic>, and <jats:italic>MYO18B<\/jats:italic>. The CIMP\u2212 subgroup, with worse prognosis, was associated with higher expression of <jats:italic>TAL1<\/jats:italic> along with frequent STIL\u2010TAL1 fusions (2\/40 in CIMP+ vs 11\/24 in CIMP\u2212), as well as stronger expression of <jats:italic>BEX1<\/jats:italic>. Altogether, our findings suggest different routes for leukemogenic transformation in the T\u2010ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.<\/jats:p>","DOI":"10.1002\/cam4.1917","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T16:25:46Z","timestamp":1545409546000},"page":"311-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["An integrated transcriptome analysis in T\u2010cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated <i>TAL1<\/i> and ANTP homeobox gene expression"],"prefix":"10.1002","volume":"8","author":[{"given":"Zahra","family":"Haider","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4r","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Ume\u00e5 University Ume\u00e5 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