Efficacy of fetinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia
- Author(s)
- Churchman, ML; Low, J; Qu, C; Paietta, EM; Kasper, LH; Chang, Y; Payne-Turner, D; Althoff, MJ; Song, G; Chen, SC; Ma, J; Rusch, M; McGoldrick, D; Edmonson, M; Gupta, P; Wang, YD; Caufield, W; Freeman, B; Li, L; Panetta, JC; Baker, S; Yang, YL; Roberts, KG; McCastlain, K; Iacobucci, I; Peters, JL; Centonze, VE; Notta, F; Dobson, SM; Zandi, S; Dick, JE; Janke, L; Peng, J; Kodali, K; Pagala, V; Min, J; Mayasundari, A; Williams, RT; Willman, CL; Rowe, J; Luger, S; Dickins, RA; Guy, RK; Chen, T; Mullighan, CG;
- 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
- Research Division(s)
- Molecular Medicine
- PubMed ID
- 26321221
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2015.07.016
- Terms of Use/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