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

Luong-Gardiol, N.; Siddiqui, I.; Pizzitola, I.; Jeevan-Raj, B.; Charmoy, M.; Huang, Y.; Irmisch, A.; Curtet, S.; Angelov, G.S.; Danilo, M.; Juilland, M.; Bornhauser, B.; Thome, M.; Hantschel, O.; Chalandon, Y.; Cazzaniga, G.; Bourquin, J.P.; Huelsken, J.; Held, W.

doi:10.1016/j.ccell.2019.03.005

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

Details

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State: Public
Version: Final published version
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Serval ID

serval:BIB_B56A0F7637FF

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Cancer cell

Author(s)

Luong-Gardiol N., Siddiqui I., Pizzitola I., Jeevan-Raj B., Charmoy M., Huang Y., Irmisch A., Curtet S., Angelov G.S., Danilo M., Juilland M., Bornhauser B., Thome M., Hantschel O., Chalandon Y., Cazzaniga G., Bourquin J.P., Huelsken J., Held W.

ISSN

1878-3686 (Electronic)

ISSN-L

1535-6108

Publication state

Published

Issued date

15/04/2019

Peer-reviewed

Oui

Volume

Number

Pages

649-663.e10

Language

english

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Abstract

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.

Keywords

Animals, Fusion Proteins, bcr-abl/genetics, Fusion Proteins, bcr-abl/metabolism, Gene Expression Regulation, Leukemic, Humans, K562 Cells, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, Survivin/genetics, Survivin/metabolism, Wnt Signaling Pathway, beta Catenin/genetics, beta Catenin/metabolism, gamma Catenin/genetics, gamma Catenin/metabolism, B cell acute lymphoblastic leukemia (B-ALL), BCR-ABL1, BIRC5 (Survivin), MYC, chronic myeloid leukemia (CML), junction plakoglobin, β-catenin, γ-catenin

URN

urn:nbn:ch:serval-BIB_B56A0F7637FF3

OAI-PMH

oai:serval.unil.ch:BIB_B56A0F7637FF

DOI

10.1016/j.ccell.2019.03.005

Pubmed

30991025

Web of science

000464931000012

Create date

28/04/2019 14:35