Efficacy of retinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia

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 were associated with acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Rexinoid receptor agonists reversed this phenotype, in part 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 m

ORGANISM(S): Mus musculus

SUBMITTER: Chunxu Qu 

PROVIDER: E-GEOD-68391 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress