小鼠模型 z-bo 2020-11-30 372

　　A research team led by Dr. Nadia Carlesso, associate professor of pediatrics at Indiana University, found that, like a series of fallen dominoes, a series of molecular events in the bone marrow can produce high levels of inflammation, which can disrupt normal blood formation and may Cause leukemia.

　　The bone marrow contains white blood cells and red blood cells produced during the hematopoietic process, and the bone marrow also provides a support system for hematopoietic cells (called the hematopoietic microenvironment). The latest research suggests that the hematopoietic microenvironment plays an important role in the process of a series of potentially fatal diseases (called myeloproliferative diseases). In fact, people have known the link between inflammation and cancer for many years. For example, it is known that high levels of inflammation in the bone marrow are associated with the development of myeloproliferative diseases, and myeloproliferative diseases can cause serious diseases due to the production of too many myeloid cells (these cells are normally used to fight off infection). These diseases bring the risk of heart attack and stroke to patients, and often develop into acute leukemia and bone marrow failure. At present, these studies lack genetic models, especially for blood-related malignancies, and there is no effective therapy to treat most myeloproliferative diseases.

　　This study aimed at the phenomenon that the Notch molecule, which plays an important role in the production of blood cells, was abnormal and reduced the expression level. The researchers used genetically modified mice to find that the absence of Notch in the hematopoietic microenvironment would trigger a series of molecular events , The result is a series of inflammatory factors. After the researchers blocked the activity of a molecule in this biochemical cascade, the myeloproliferative disease in mice was reversed. In addition, the level of this molecule in human patients with myeloproliferative disease has also been significantly increased. These findings suggest that the development of drugs for different key points in the immune response process may be a potential strategy for the treatment of myeloproliferative diseases. Carlesso said that another key finding of this study is that the molecular chains that cause inflammation do not occur directly in bone marrow hematopoietic cells, but in cells that make up the bone marrow microenvironment, especially endothelial cells.

　　This work suggests that people not only need to target tumor cells, but also cells in the inflammatory microenvironment surrounding tumor cells. Researchers believe that this strategy will show efficacy in preventing the progression of myeloproliferative diseases and the metastasis of acute leukemia. Dr. Carlesso also pointed out that Notch molecules are mostly called proto-oncogenes, so past studies have often targeted Notch gene therapy. The study suggests that doctors need to realize that lowering the level of Notch function can inhibit the progression of blood diseases.