Metabolic reprogramming is a key hallmark of cancer, but less is known about metabolic plasticity of the same tumor at different sites. Here, we investigated the metabolic adaptation of leukemia in two different microenvironments, the bone marrow and the central nervous system (CNS). We identified a metabolic signature of fatty acid synthesis in CNS leukemia, highlighting stearoyl-CoA desaturase (SCD) as a key player. In vivo SCD overexpression increases CNS disease, whereas genetic or pharmacological inhibition of SCD decreases CNS load. Overall, we demonstrated that leukemic cells dynamically rewire metabolic pathways to suit local conditions and that targeting these adaptations can be exploited therapeutically.

代谢重编程是癌症的一个关键标志，但人们对同一肿瘤在不同部位的代谢可塑性知之甚少。在这里，我们研究了白血病在两种不同微环境（骨髓和中枢神经系统（CNS））中的代谢适应。我们确定了中枢神经系统白血病中脂肪酸合成的代谢特征，强调硬脂酰辅酶A去饱和酶（SCD）是关键参与者。体内 SCD 过度表达会增加 CNS 疾病，而 SCD 的遗传或药理学抑制会降低 CNS 负荷。总体而言，我们证明白血病细胞动态地重新连接代谢途径以适应当地条件，并且可以在治疗上利用针对这些适应的目标。