Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/107163
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Type: Journal article
Title: Efficacy of retinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia
Author: Churchman, M.
Low, J.
Qu, C.
Paietta, E.
Kasper, L.
Chang, Y.
Payne-Turner, D.
Althoff, M.
Song, G.
Chen, S.-C.
Ma, J.
Rusch, M.
McGoldrick, D.
Edmonson, M.
Gupta, P.
Wang, Y.-D.
Caufield, W.
Freeman, B.
Li, L.
Panetta, J.
et al.
Citation: Cancer Cell, 2015; 28(3):343-356
Publisher: Cell Press
Issue Date: 2015
ISSN: 1535-6108
1878-3686
Statement of
Responsibility: 
Michelle L. Churchman, Jonathan Low, Chunxu Qu, Elisabeth M. Paietta, Lawryn H. Kasper ... Charles G. Mullighan ... et al.
Abstract: Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.
Keywords: Fusion Proteins, bcr-abl
Rights: Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ccell.2015.07.016
Published version: http://dx.doi.org/10.1016/j.ccell.2015.07.016
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