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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 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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