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Previously, using an integrated genomic analysis of matched diagnosis\u2010relapse paired samples, we identified overactivation of the Wnt pathway as a possible mechanism of recurrence. To validate these findings and document whether Wnt inhibition may sensitize cells to chemotherapy, we analysed the expression of activated \u03b2\u2010catenin (and its downstream target\n                    <jats:italic>BIRC5<\/jats:italic>\n                    ) using multiparameter phosphoflow cytometry and tested the efficacy of a recently developed Wnt inhibitor,\n                    <jats:styled-content style=\"fixed-case\">iCRT<\/jats:styled-content>\n                    14, in\n                    <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>\n                    cell lines and patient samples. We observed increased activation of \u03b2\u2010catenin at relapse in 6\/10 patients. Furthermore, treatment of leukaemic cell lines with\n                    <jats:styled-content style=\"fixed-case\">iCRT<\/jats:styled-content>\n                    14 led to significant downregulation of Wnt target genes and combination with traditional chemotherapeutic drugs resulted in a synergistic decrease in viability as well as a significant increase in apoptotic cell death. Finally, pre\u2010treatment of purified blasts from patients with relapsed leukaemia with the Wnt inhibitor followed by exposure to prednisolone, restored chemosensitivity in these cells. Our results demonstrate that overactivation of the Wnt pathway may contribute to chemoresistance in relapsed childhood\n                    <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>\n                    and that Wnt\u2010inhibition may be a promising therapeutic approach.\n                  <\/jats:p>","DOI":"10.1111\/bjh.13011","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T02:04:07Z","timestamp":1404439447000},"page":"87-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"167","author":[{"given":"Smita","family":"Dandekar","sequence":"first","affiliation":[{"name":"NYU Langone Medical Center NYU Cancer Institute New York NY 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