Oncogenic cooperation between TAL1 expression and AKT pathway activation in T-cell acute lymphoblastic leukemia
TAL1 is an oncogene that is ectopically expressed in about one third of T-ALL patients and these cases often also harbor additional mutations that lead to activation of the PI3K/AKT signaling pathway. TAL1 acts as a transcription factor that regulates the expression of many other genes, but it remains unknown how TAL1 cooperates with PI3K/AKT pathway activation and how this cooperation supports leukemia development. In this project we aim to determine the molecular mechanism responsible for the cooperation between TAL1 and PI3K/AKT. We will develop novel cell models and novel mouse models and use T-ALL leukaemia cells from patients. Using integrated analysis of binding of transcription factors to DNA, analysis of these transcriptional complexes and gene expression analysis, we hope to get more in-depth insight in the molecular mechanisms leading to T-cell transformation. These data can also lead to the identification of novel targets for therapy.