Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.

Cancer Cell 2015 Sep 27;28(3):343-56. Epub 2015 Aug 27.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address:

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.

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http://www.cell.com/cancer-cell/pdf/S1535-6108(15)00268-8.pd
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http://linkinghub.elsevier.com/retrieve/pii/S153561081500268
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http://dx.doi.org/10.1016/j.ccell.2015.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573904PMC
September 2015
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