ARIEL (ARID5B-inducing enhancer-associated long noncoding RNA/XLOC_005968) acts as an eRNA in a subset of TAL1-type T-ALL. The TAL1 complex in T-ALL consists of several transcriptional regulators that include the class II basic helix-loop-helix transcription factor TAL1, E proteins (eg, E47 or HEB), LIM-only proteins (eg, LMO1/2), and GATA factors (eg, GATA3). This complex frequently co-occupies enhancers with partner transcription factors ARID5B, RUNX1, and MYB. In the nucleus, the TAL1 complex instructs RNA polymerase II (RNAPII) to transcribe ARIEL from the ARID5B enhancer template located at −135 kb relative to the ARID5B transcriptional start site.1,6 ARIEL connects the enhancer to MED12, a subunit of the mediator coactivator complex that binds RNAPII. Thus, ARIEL facilitates chromatin looping interactions between the enhancer and the ARID5B promoter. These interactions in turn promote the expression of ARID5B, which amplifies positive autoregulatory loops that generate the TAL1 oncogenic transcriptional program.7,8 Upregulated expression of ARID5B target genes promotes ARIEL transcription. In this diagram, direct interactions involving ARIEL and genomic coordinates of factors are postulated.