Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome.

ABSTRACT: Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1⁺ (Ph⁺) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionaril

SUBMITTER: Witkowski MT 

PROVIDER: S-EPMC5339666 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature