da Conceição Barbosa Thayana, Poubel Caroline Pires, Maciel Ana Luiza Tardem, Blunck Caroline Barbieri, Dos Santos Rafael Lima, Boroni Mariana, Mansur Marcela Braga, Emerenciano Mariana
Genetics of Acute Leukaemia Laboratory (GenLAb), Research Centre, Instituto Nacional de Câncer (INCA), Rua André Cavalcanti, 37, 6th Floor, Rio de Janeiro, RJ, 20231-050, Brazil.
Bioinformatics and Computational Biology Lab, Research Centre, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Sci Rep. 2025 Aug 9;15(1):29153. doi: 10.1038/s41598-025-10262-0.
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.
GATA3非编码变体rs3824662与Ph样B-ALL的发病机制有关，在该疾病中，它与广泛的染色质重组相关，导致多个基因失调，包括CRLF2过表达。鉴于与rs3824662变体相关的染色质景观改变以及GATA3结合区域的可及性增加，我们研究了位于GATA3基因座附近的增强子RNA（eRNA）在调节CRLF2表达中的潜在作用。我们发现，位于chr10:8,443,562-8,449,563的eRNA_G3的表达与CRLF2表达呈正相关。值得注意的是，在携带GATA3 rs3824662变体的Ph样ALL病例中，eRNA_G3显著上调。这些发现表明，rs3824662和eRNA可能共同参与了调控Ph样ALL中GATA3和CRLF2表达的机制。
