Deciphering the "black box" of white blood cells apoptosis, scientists find potential new target for myeloid leukemia

Not long ago, Professor Fu Caiyun of Zhejiang University of Technology found for the first time that neurotrophic peptide receptor 1 (NK-1R) showed significantly high expression in peripheral blood of myeloid leukemia patients, and revealed that targeted blocking NK-1R can cause endoplasion stress and lead to the new molecular mechanism of apoptosis in myeloid leukemia cells caused by overloaded oxidative stress caused by mitochondrial calcium, providing an effective basis for the precise treatment of myeloid leukemiaThe research paper was recently published in the Proceedings of the National Academy of Sciencespotential new targets are found, it is expected to hit the key" in the basic research field, the molecular mechanism of the development of myeloid leukemia needs to be further clarified, the treatment of key technologies and the excavation of new targets also need to be breakthroughThe development of more effective myeloid leukemia treatment drugs is a scientific problem that needs to be solved urgently in the basic research and clinical practice of myeloid leukemiaFu Caiyun introduced, the premise of precision medical is to find a precise target, that is, the body's diseased proteinTumor cells, compared with normal cells, must have some mutations or abnormal protein expression targetsWhich targets can be effectively promoted to clinical treatment targets in the future? That's the direction the team has been trying to findby working with local hospitals to collect clinical samples, and to compare the differences in protein expression in peripheral blood in normal people and leukemia patients, Fu Caiyun team found that NK-1R membrane protein showed significant high expression in the peripheral blood and myeloid leukemia cell lines of myeloid leukemiaWhat is the significance of the pathology of this high expression? For this reason, the team selected two molecularally distinct antagonists to block the NK-1R receptor, and found that under the action of antagonists, nk-1R signaling pathways were blocked, leukemia cells showed slow proliferation, and apoptotic cell death"This suggests that both antagonists have a very good effect on the growth of myeloid leukemiaFu Explainsstudies also found that NK-1R antagonists, in addition to inducing myeloid leukemia apoptosis, also have the effect of relieving cancer pain at animal levels"These findings suggest that NK-1R is a potential new target for myeloid leukemia treatmentFu Caiyun said, this is like finding a difficult to find an enemy, find the target, in order to hit the keyto decipher the mystery of apoptosis and lay the foundation for the development of clinical new drugs
discovering the potential new target of NK-1R, fu Caiyun team further began to study molecular mechanisms She told reporters that from the perspective of basic research, the study of drug molecular mechanism is very important, if there is no good molecular mechanism to support the results of the study, clinical applicationonce once out of the question, often difficult to deal with " If leukaemia cells apoptosis occurs after passing through a 'black box', then all we have to do now is study what's going on in the black box, which is how the antagonists act on the new target, thus leading to the death of leukemia cells." Fu said after follow-up research, the team to a certain extent to decipher the secret of myeloid leukemia apoptosis They found that the cell membrane receptor NK-1R, which is involved in a variety of physiological pathological regulation, when combined with antagonists, causes the calcium content in the cell to rise, which causes the calcium in the mitochondrial body to rise rapidly, which leads to mitochondrial dysfunction Once the function of mitochondria is disturbed, the reactive oxygen in the cell cannot be used effectively As the amount of reactive oxygen in the cell increases, reactive oxygen actively cuts DNA, causing DNA damage reaction, which leads to apoptosis of leukemia cells in addition, , the team further evaluated the anti-tumor effect and its safety of NK-1R antagonists in vitro and in vitro Aripitan, one of two NK-1R antagonists selected by Fu Caiyun, has been approved by the U.S FDA for treatment of nausea and vomiting after chemotherapy, and safety has been proven it is understood that the results of the project are of great significance for the smooth promotion of NK-1R antagonists for the treatment of clinical myeloid leukemia If subsequent clinical studies further confirm their effects, the new molecular mechanism will provide a solid foundation for the development of new clinical drugs.