|Jia Wei and Chen Saijuan cooperated in leukemia and had new findings|
Professor Jia Wei from the sixth people‘s hospital medical center andprofessor sai-juan Chen from the Shanghai institute of hematology cooperated in acute myelogenous leukemia (AML) cells with strong ability of fructose metabolism, and active metabolism of fructose promote malignant progress of leukemia. The results of the study, published online on October 13 in Cancer research field top academic journal Cancer Cell (link is: http://www.cell.com/cancer-cell/fulltext/S1535-6108 (16), 30441 - X), a research paper on the topic of “Enhanced fructose utilization mediated by SLC2A5 is a unique metabolic feature of acute myeloid leukemia with therapeutic potential”. Professor Jia Wei and professor sai-juan Chen areco-author of this paper common communication. Dr Chen Wenlian, Dr Wang Yueying and Dr Zhao Aihua are common first authors of this paper.
The above two team cooperation, in the international academic journals in 2014 for “(BLOOD magazine) published on acute myelogenous leukemia (metabolomics research work. Study found that patients with AML overall metabolic spectrum significant changes, through top-down (Top - down approach) systems biology research train of thought, the team found that patients with AML of glycolysis metabolism are very active, and patients of glycolysis metabolic activity are higher, with worse survival. The team also found that the activity of glycolysis metabolism can significantly reduce the sensitivity of AML cells of cytarabine effective. Researchers have observed in the later work, that active AML cells of glycolysis metabolism can lead to a serious shortage of glucose levels in the bone marrow microenvironment, and this kind of circumstance how to keep plenty of AML cells carbon source intake to maintain cell malignant proliferation may be an important metabolic mechanisms of cancer. Along with the further research, they got an important discovery: under the condition of the lack of glucose, AML cells can activate an alternative mechanism to use of fructose. Fructose is the second largest blood sugar, blood in the system of its cell membrane transporter by GLUT5 SLC2A5 genes encoding proteins mediated. The team found that SLC2A5 gene level, the higher the AML cells expressed (that is, the use of the stronger the ability of fructose), is the prognosis of patients. Use of RNA silencing technology interfere with AML cells SLC2A5 gene expression, can significantly reduce the cell of fructose intake and fructose to induce cell proliferation. Found here, on the basis of the research team used a small molecule drugs to block specific fructose across the plasma membrane, the measure to restrain the fructose use can significantly inhibit cell in vitro cell model of malignant proliferation and invasion. In animal models of AML, use the small molecule drugs to block fructose AML cells across the plasma membrane can significantly improve the symptoms of leukemia in mice and prolong the survival of mice. Notable is, the small molecule drugs and cytarabine effective synergy, further improve the therapeutic effect.
This work has revealed that in addition to glucose, fructose is AML cells of another important energy material. Responsible for fructose transfer and utilization of transporter proteins GLUT5, is a new target for the treatment of AML. Such a characteristic of fructose metabolism phenotype is likely to exist in AML other cancer cells, and in view of the small molecule GLUT5 chemical drugs or antibodies, is expected to be with the common tumor chemotherapy drugs (such as cytarabine) joint use, which will greatly improve the therapeutic effect of cancer patients.