Enhancer RNAs contribute to genome reprogramming driven by a GATA3 noncoding variant in leukaemia

The GATA3 noncoding variant rs3824662 has been implicated in the pathogenesis of Ph-like B-ALL, where it is associated with extensive chromatin reorganisation, resulting in the dysregulation of multiple genes, including CRLF2 overexpression. Given the altered chromatin landscape and increased accessibility of GATA3 binding regions associated with the rs3824662 variant, we investigated the potential role of enhancer RNAs (eRNAs) located near the GATA3 locus in regulating CRLF2 expression. We found that the expression of eRNA_G3, located at chr10:8,443,562-8,449,563, was positively correlated with CRLF2 expression. Notably, eRNA_G3 was significantly upregulated in Ph-like ALL cases carrying the GATA3 rs3824662 variant. These findings suggest that both rs3824662 and eRNAs may cooperatively contribute to the regulatory mechanisms governing GATA3 and CRLF2 expression in Ph-like ALL.