T cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy strongly affected by the abnormal activity of transcription factors. Here we report a high expression of developmental transcription factor SIX6 in TAL1 subtype of T-ALL. Our data indicates that this high expression is directly regulated by binding of TAL1 and GATA3 transcription factors into an upstream enhancer element. We also looked into the potential targets of SIX6 in T-ALL and Crispr-cas9 mediated knockout of SIX6 in Jurkat cells caused significant changes in the expression of multiple genes, including genes related to mTOR signaling. In two independent patient cohorts, the high SIX6 expression shows a trend of less favourable prognosis. However, the knockout of SIX6 was not enough to have an effect on proliferation, cell cycle or viability of the Jurkat cells and overexpression of SIX6 in the T-ALL zebrafish model didnt influence the progression of the disease. Our results show that high expression of SIX6 has a trend towards a less favourable outcome, but SIX6 doesnt have an independent oncogenic role in T-ALL. SOURCE: Laura Oksa (laura.oksa@tuni.fi) - Hemato-Oncology Research Group Tampere University

Pluto Bioinformatics

GSE148658: SIX6 knockdown in Jurkat-Cas9 T-ALL cell line