Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia.

ABSTRACT: While childhood acute lymphoblastic leukaemia (ALL) is now highly curable, the dismal prognosis for children who relapse warrants novel therapeutic approaches. Previously, using an integrated genomic analysis of matched diagnosis-relapse 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 β-catenin (and its downstream target BIRC5) using multiparameter phosphoflow cytometry and tested the efficacy of a recently developed Wnt inhibitor, iCRT14, in ALL cell lines and patient samples. We observed increased activation of β-catenin at relapse in 6/10 patients. Furthermore, treatment of leukaemic cell lines

SUBMITTER: Dandekar S 

PROVIDER: S-EPMC4207443 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature