Chen Wen-Lian, Wang Yue-Ying, Zhao Aihua, Xia Li, Xie Guoxiang, Su Mingming, Zhao Linjing, Liu Jiajian, Qu Chun, Wei Runmin, Rajani Cynthia, Ni Yan, Cheng Zhen, Chen Zhu, Chen Sai-Juan, Jia Wei
State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Cancer Cell. 2016 Nov 14;30(5):779-791. doi: 10.1016/j.ccell.2016.09.006. Epub 2016 Oct 13.
Rapidly proliferating leukemic progenitor cells consume substantial glucose, which may lead to glucose insufficiency in bone marrow. We show that acute myeloid leukemia (AML) cells are prone to fructose utilization with an upregulated fructose transporter GLUT5, which compensates for glucose deficiency. Notably, AML patients with upregulated transcription of the GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of the antileukemic agent, Ara-C. In conclusion, this study highlights enhanced fructose utilization as a metabolic feature of AML and a potential therapeutic target.
快速增殖的白血病祖细胞消耗大量葡萄糖，这可能导致骨髓中葡萄糖不足。我们发现急性髓系白血病（AML）细胞易于利用果糖，果糖转运体GLUT5上调，从而补偿葡萄糖缺乏。值得注意的是，编码GLUT5的基因SLC2A5转录上调或果糖利用增加的AML患者预后较差。果糖摄取的药理学阻断可改善白血病表型，并增强抗白血病药物阿糖胞苷的细胞毒性。总之，本研究强调果糖利用增强是AML的一种代谢特征和潜在治疗靶点。
