γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Article Article scientifique Article γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia eng 2019 author Luong-Gardiol Noemie author Siddiqui Imran author Pizzitola Irene author Jeevan-Raj Beena author Charmoy Mélanie author Huang Yuna 775957 author Irmisch Anja author Curtet Sara author Angelov Georgi S author Danilo Maxime author Juilland Mélanie author Bornhauser Beat author Thome Margot author Hantschel Oliver author Chalandon Yves 0000-0001-9341-8104 644957 author Cazzaniga Gianni author Bourquin Jean-Pierre author Huelsken Joerg author Held Werner 649-663.e10 10.1016/j.ccell.2019.03.005 30991025 1535-6108 The 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-ABL1 BIRC5 (Survivin) MYC Chronic myeloid leukemia (CML) Junction plakoglobin Β-catenin γ-catenin Dewey 616 Swiss National Science Foundation Role of canonical Wnt signals for the development, homeostasis and differentiation of NK cells and CD8 T cells 159598 CH Project funding Swiss National Science Foundation The leukemia initiating cell compartment in childhood acute lymphoblastic leukemia: clonal composition and interactions with the microenvironment 133108 CH Project funding Swiss National Science Foundation Identification et caractérisation de substrats de la protéase MALT1 166627 CH Project funding Swiss National Science Foundation Targeting Wnt signaling in Leukemia 136245 CH Programmes Swiss National Science Foundation Generation and maintenance of conventional and unconventional memory CD8 T cells 179570 CH Project funding 56 Département de médecine 221 false 1216 Leucémie et transplantation allogénique de cellules souches hématopoïétiques 982 Cancer Cell 35 4 c1acfb3b-1eb5-405f-8e1a-84d3548e2e2f Article (Published version) Restricted 1-s2.0-S1535610819301503-main.pdf 4515585 application/pdf a85cf6f8-e012-40e4-8acd-1b9704e19dd3 Supplemental data Restricted ScienceDirect_files_03May2020_09-11-29.772.zip 19205658 application/zip restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia	Cancer Cell			2019	300	0

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Huang, Yuna