Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and...Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and activation of B-cell malignancies.Genetic alterations and other mechanisms resulting in constitutive activation,rearrangement,or mutation of MYC and TP53 contribute to the development of lymphomas,progression and therapy resistance by gene dysregulation,activation of downstream anti-apoptotic pathways,and unfavorable microenvironment interactions.The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas.In this review,we present the physiological roles of Myc and p53 proteins,and recent advances in understanding the pathological roles of Myc,p53,and their cross-talk in lymphoid neoplasms.In addition,we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways.Although,to date,these trials have failed to overcome drug resistance,the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.展开更多
Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to th...Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.展开更多
基金This work was supported by the National Natural Science Foundation of China 81460030 and 81770221 to LY.
文摘Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and activation of B-cell malignancies.Genetic alterations and other mechanisms resulting in constitutive activation,rearrangement,or mutation of MYC and TP53 contribute to the development of lymphomas,progression and therapy resistance by gene dysregulation,activation of downstream anti-apoptotic pathways,and unfavorable microenvironment interactions.The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas.In this review,we present the physiological roles of Myc and p53 proteins,and recent advances in understanding the pathological roles of Myc,p53,and their cross-talk in lymphoid neoplasms.In addition,we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways.Although,to date,these trials have failed to overcome drug resistance,the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.
基金This work was supported by fundings from the National Natural Science Foundation of China(82070217 and 81873427,toDr.JiaWei,81770211,toDr.Min Xiao,81670152,to Dr.Liang Huang,and 81700145 to Dr.Li Yang)fundings from the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.Jianfeng Zhou)funding from CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.JiaWei).
文摘Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.
