T 细胞急性淋巴细胞白血病 (T-ALL) 是一种免疫系统癌症。大约 20% 的儿童和 50% 的成人 T-ALL 患者患有难治性疾病或复发并死于该疾病。为了改善患者的治疗效果，需要新的疗法。为了确定新的治疗靶点，我们结合了 T-ALL 基因表达和代谢的分析，以确定 T-ALL 细胞表现出的代谢适应。我们发现谷氨酰胺的摄取对于 T-ALL 增殖至关重要。同位素示踪实验表明，谷氨酰胺通过 TCA 循环为天冬氨酸合成提供燃料，并且谷氨酰胺和谷氨酰胺衍生的天冬氨酸共同提供嘌呤中的三个氮原子以及嘧啶环中除一个原子之外的所有氮原子。我们发现，通常在中枢神经系统中表达的谷氨酸-天冬氨酸转运蛋白 EAAT1 (SLC1A3) 对于谷氨酰胺转化为天冬氨酸和核苷酸至关重要，并且 T-ALL 细胞增殖依赖于 EAAT1 功能。通过这项工作，我们将 EAAT1 确定为 T-ALL 治疗的新治疗靶点。

T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.