Survival and Proliferation of T-cell Acute Lymphoblastic Leukaemia Depends on mTOR-regulated Glutamine Uptake and EAAT1 Activity

With the aim to identify new therapeutic targets for T-ALL treatment, we integrated transcriptomics and metabolomics data, including live-cell NMR-spectroscopy, of cell lines and patient samples. We found that T-ALL cells have limited energy availability, resulting in down-regulated mTOR-signalling and reduced autophagy. Despite this, mTOR kinase activity is essential for the glutamine-uptake and rapid proliferation. T-ALL cells use glutamine as a source for all nitrogen atoms in purines and for all but one carbon in pyrimidines. We show that EAAT1, the glutamate-aspartate transporter normally only expressed in the CNS, is a crucial facilitator of the glutamine conversion to nucleotides. T-ALL cell proliferation depends on EAAT1 function, identifying it as a target for T-ALL treatment. Overall design: RNAseq (paired end) of ARR, DU.528, HSB2 and CCRF-CEM cell lines in duplicate.