Efficacy of fetinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia
Journal Title
Cancer Cell
Publication Type
Journal Article in press
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.
Publisher
Cell Press
WEHI Research Division(s)
Molecular Medicine
PubMed ID
26321221
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-09-24 02:12:22
Last Modified: 2015-09-24 02:22:16
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