Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were...Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were randomly divided into the observation group and the control group. 80 patients in the control group were treated with CAG treatment scheme, and 80 patients in the observation group were treated with decitabine on the basis of CAG treatment scheme. The final treatment effect of the two groups of patients was compared. Results: the therapeutic effect of the observation group was better than that of the control group. In contrast, the effective rate of 82.50% in the observation group was higher than that of 67.50% in the other group;There was no difference in the incidence of adverse reactions between the two groups. Conclusion: CAG combined with decitabine is effective in the treatment of relapsed refractory acute myeloid leukemia. The quality of life of the patients can be effectively improved. Compared with the previous patients, they have a higher degree of life comfort. The disease control effect of the patients is better, and the adverse reactions are also within the controllable range.展开更多
Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer'...Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,Huntington's disease,metabolic dysfunction-associated steatohepatitis,heart failure,and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer.Thus,understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies.Here,we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases.We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options.In addition,we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.展开更多
Acute myeloid leukemia(AML)is a common hematological malignancy with overall poor prognosis.Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory(RR)AML patients.Th...Acute myeloid leukemia(AML)is a common hematological malignancy with overall poor prognosis.Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory(RR)AML patients.Through clinical specimens,animal models and cell-level studies,we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1(HMGCS1)in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation,increase chemotherapy sensitivity and improve the occurrence and development of AML.Here,we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival(OS).Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity,while stable overexpression of HMGCS1 had the opposite effects.Mechanistically,we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase(MAPK)pathway activity,while overexpression of HMGCS1 could remarkably enhance the pathway.U0126,a MEK1 inhibitor,offset the effects of HMGCS1 overexpression,indicating that HMGCS1 promotes RR AML through the MAPK pathway.Further,we verified that hymeglusin,a specific inhibitor of HMGCS1,decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients.Furthermore,combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin(ADR)had synergistic toxic effects on AML cells.Our study demonstrates the important role of HMGCS1 in AML,and targeting this protein is promising for the treatment of RR AML.展开更多
文摘Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were randomly divided into the observation group and the control group. 80 patients in the control group were treated with CAG treatment scheme, and 80 patients in the observation group were treated with decitabine on the basis of CAG treatment scheme. The final treatment effect of the two groups of patients was compared. Results: the therapeutic effect of the observation group was better than that of the control group. In contrast, the effective rate of 82.50% in the observation group was higher than that of 67.50% in the other group;There was no difference in the incidence of adverse reactions between the two groups. Conclusion: CAG combined with decitabine is effective in the treatment of relapsed refractory acute myeloid leukemia. The quality of life of the patients can be effectively improved. Compared with the previous patients, they have a higher degree of life comfort. The disease control effect of the patients is better, and the adverse reactions are also within the controllable range.
基金supported by the National Natural Science Foundation of China(82471593 to J.M.32330047,31930057 to F.W.)。
文摘Both iron metabolism and ferroptosis(an iron-dependent form of programmed cell death)have been connected to the development and progression of many currently incurable non-communicable diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,Huntington's disease,metabolic dysfunction-associated steatohepatitis,heart failure,and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer.Thus,understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies.Here,we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases.We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options.In addition,we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.
基金supported by the National Natural Science Foundation of China to H.Z.(Grant Nos.81770184,81970143,and 82270167)and L.Z.(Grant No.81800174)the Talent Young Program of Guangdong Province(2021B1515020017),and the Leading Talents Program from The First Affiliated Hospital of Jinan University to H.Z.
文摘Acute myeloid leukemia(AML)is a common hematological malignancy with overall poor prognosis.Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory(RR)AML patients.Through clinical specimens,animal models and cell-level studies,we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1(HMGCS1)in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation,increase chemotherapy sensitivity and improve the occurrence and development of AML.Here,we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival(OS).Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity,while stable overexpression of HMGCS1 had the opposite effects.Mechanistically,we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase(MAPK)pathway activity,while overexpression of HMGCS1 could remarkably enhance the pathway.U0126,a MEK1 inhibitor,offset the effects of HMGCS1 overexpression,indicating that HMGCS1 promotes RR AML through the MAPK pathway.Further,we verified that hymeglusin,a specific inhibitor of HMGCS1,decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients.Furthermore,combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin(ADR)had synergistic toxic effects on AML cells.Our study demonstrates the important role of HMGCS1 in AML,and targeting this protein is promising for the treatment of RR AML.
