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Relapsed ALL is a leading cause of death in young people, and further improvements in outcome will required the development of therapeutic approaches directed against rational therapeutic targets, as escalation of the intensity of existing therapies is limited by toxicity. This review summarizes advances in the biology and treatment of HR and relapsed ALL presented at a symposium at the 2010 American Society for Pediatric Hematology and Oncology Annual Meeting. Analysis of large patient cohorts has identified several factors associated with HR of relapse including older age, T\u2010lineage disease, and persisting minimal residual disease (MRD) early in therapy. As the results of salvage therapy remain poor, new treatment approaches are needed. BCR\u2010ABL1\u2010positive (Ph+) ALL has historically had a very poor outcome, but recent studies have demonstrated the impressive improvements in treatment outcome with the use of tyrosine kinase inhibitors (TKIs). High\u2010resolution genomic profiling of genetic alterations and gene expression has revolutionized our understanding of the genetic basis of ALL, and has identified several alterations associated with poor outcome, including mutations of the lymphoid transcription factor gene <jats:italic>IKZF1<\/jats:italic> (IKAROS), activating mutations of Janus kinases, and rearrangement of the lymphoid cytokine receptor gene <jats:italic>CRLF2<\/jats:italic>. These data indicated that the genetic basis of HR\u2010ALL is multifactorial, and have also provided a new potential therapeutic option directed at JAK inhibition. Pediatr Blood Cancer 2011;56:984\u2013993. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/pbc.22996","type":"journal-article","created":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T21:39:28Z","timestamp":1297805968000},"page":"984-993","source":"Crossref","is-referenced-by-count":52,"title":["Improving outcomes for high\u2010risk ALL: Translating new discoveries into clinical care"],"prefix":"10.1002","volume":"56","author":[{"given":"Stephen P.","family":"Hunger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Raetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mignon L.","family":"Loh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles 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