Luong-Gardiol, NoemieSiddiqui, ImranPizzitola, IreneJeevan-Raj, BeenaCharmoy, MélanieHuang, YunIrmisch, AnjaCurtet, SaraAngelov, Georgi S.Danilo, MaximeJuilland, MélanieBornhauser, BeatThome, MargotHantschel, OliverChalandon, YvesCazzaniga, GianniBourquin, Jean-PierreHuelsken, JoergHeld, Werner2019-04-302019-04-302019-04-302019-04-1510.1016/j.ccell.2019.03.005https://infoscience.epfl.ch/handle/20.500.14299/15616330991025The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ-catenin in the initiation and maintenance of BCR-ABL1 + B-ALL but not CML. The selectivity was explained by a partial γ-catenin dependence of MYC expression together with the susceptibility of B-ALL, but not CML, to reduced MYC levels. MYC and γ-catenin enabled B-ALL maintenance by augmenting BIRC5 and enforced BIRC5 expression overcame γ-catenin loss. Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1 + B-ALL.B cell acute lymphoblastic leukemia (B-ALL)BCR-ABL1BIRC5 (Survivin)MYCchronic myeloid leukemia (CML)junction plakoglobinβ-cateninγ-catenintext::journal::journal article::research article