| First Author | Grzes KM | Year | 2017 |
| Journal | Leukemia | Volume | 31 |
| Issue | 12 | Pages | 2771-2779 |
| PubMed ID | 28546582 | Mgi Jnum | J:252435 |
| Mgi Id | MGI:6103351 | Doi | 10.1038/leu.2017.160 |
| Citation | Grzes KM, et al. (2017) Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy. Leukemia 31(12):2771-2779 |
| abstractText | This study explores the regulation and importance of System L amino acid transport in a murine model of T-cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1alpha (HIF1alpha) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1alpha or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN(-/-) T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T-cell malignancies, highlighting how a single amino acid transporter can have a key role. |
