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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE101566 | GEO | 2020/11/01

REPOSITORIES: GEO

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