Effect of depletion of BCAT1 on gene expression during NOTCH1-dependent leukemia development in the mouse

High levels of branched-chain amino acid (BCAA) transaminase 1 (Bcat1) have been associated with adverse prognosis and drug resistance in several cancer types. However, the mechanistic role of Bcat1 in T-cell acute lymphoblastic leukemia (T-ALL) development is ill defined. Here, we used a mouse T-ALL model to show that Bcat1 is required for T-ALL development and maintenance. Using a NOTCH1 gain-of-function retroviral model of T-ALL, mouse cells genetically deficient for Bcat1 showed defects in developing leukemia. Amongst the pathways upregulated in Bcat1 KO delta E-NOTCH1 cells we found “DNA repair”, “apoptosis”, and “p53 pathway”. We thus hypothesize that Bcat1 may be implicated in cell cycle progression or apoptosis of T-ALL cells. Overall design: To investigate the functional consequences of Bcat1 depletion in T-ALL cells we used a NOTCH1 gain-of-function retroviral model of T-ALL (delta E-NOTCH1). Mouse leukemia cells genetically proficient (WT) or deficient for Bcat1 (KO) were obtained. Further, mouse leukemia cells proficient for Bcat1 were treated with a Bcat1 specific inhibitor (ERG-245) or vehicle as control (PBS). We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 different samples. Comparative gene expression profiling analysis of RNA-seq data for deltaE-NOTCH1 tumors proficient (WT) or deficient (KO) or treated with a Bcat1 specific inhibitor (ERG-245).