T-cell acute lymphoblastic leukemia (T-ALL) is caused by the oncogenic transformation of developing
thymocytes. Different genetic lesions have been identified as driving events, some of which mark
genetic subgroups with distinct gene activity patterns (e.g. TLX1/3, TAL1/2, LMO1/2, HOXA).
Recently, the host lab has shown that next to protein coding genes, also long non-coding RNAs can
play a role in the development of T-ALL. In this project, we will study the role of TLX1 in the
activation of long non-coding RNAs. TLX1 is a transcription factor that is normally not expressed in
thymocytes. In T-ALL, TLX1 often binds together with other strong transcription factors outside
promotor and coding regions, that are shown to be involved in the regulation of neighbouring genes
and are called (super-) enhancers. Recent studies have shown that long noncoding RNAs can be
expressed from these enhancer regions (eRNAs) and that these eRNAs are involved in bringing the
enhancer site and its binding transcription factors in close contact with the neighboring gene
promotor. In this project, we will specifically look for TLX1-driven long non-coding RNAs that are
expressed from these enhancer sites and that help TLX1 in the repression of tumor suppressor
genes in their vicinity. This will (1) allow us to get more insights into the TLX1 oncogenic activity in TALL
and (2) explore the possibility to use RNA-based therapeutics in TLX1-driven T-ALLs.