BACKGROUND The prognosis of paediatric primary refractory/relapsed acute myeloid leukaemia(R/R AML)remains poor.Intensive therapy is typically used as salvage treatment for those with R/R AML.No data are currently ava...BACKGROUND The prognosis of paediatric primary refractory/relapsed acute myeloid leukaemia(R/R AML)remains poor.Intensive therapy is typically used as salvage treatment for those with R/R AML.No data are currently available about the use of the CLAG-M protocol as salvage therapy in paediatric patients with R/R AML.CASE SUMMARY An 8-year-old patient was diagnosed with acute myeloid leukaemia by bone marrow morphology and immunophenotype.The patient showed poor response to two cycles of induction therapy with 60%blast cells in the bone marrow after the second induction cycle.The patient achieved complete remission after being treated with the CLAG-M protocol as salvage therapy before undergoing umbilical cord blood stem cell transplantation.Morphological complete remission with haematological recovery has hitherto been maintained over 4 mo.Abnormal gene mutations detected at diagnosis were undetectable after haematopoietic stem cell transplantation.CONCLUSION Here we present a paediatric patient with primary refractory acute myeloid leukaemia who was successfully treated with the CLAG-M protocol.Given the positive results of the presented patient,large-scale clinical studies are required to assess the role of the CLAG-M protocol in the salvage treatment of refractory or relapsed AML in childhood.展开更多
The important aim in cancer treatment is the selective killing of cancer cells without damaging healthy cells and the most commonly used chemotherapy for eliminating cancer is achieved by activating the mitochondrial ...The important aim in cancer treatment is the selective killing of cancer cells without damaging healthy cells and the most commonly used chemotherapy for eliminating cancer is achieved by activating the mitochondrial apoptotic pathway. Therefore, identification of new agents that can selectively kill cancer cells becomes crucial in cancer clinical treatment.展开更多
Acute myeloid leukaemia(AML) is the most common form of acute leukaemia in adults,with increasing incidence with age and a generally poor prognosis.Almost 20% of AML patients express mutant isocitrate dehydrogenase 2(...Acute myeloid leukaemia(AML) is the most common form of acute leukaemia in adults,with increasing incidence with age and a generally poor prognosis.Almost 20% of AML patients express mutant isocitrate dehydrogenase 2(mIDH2),which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate(2-HG),resulting in poor prognosis.Thus,global institutions have been working to develop mIDH2 inhibitors.SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised.We have conducted a comprehensive study on its pharmacodynamics,pharmacokinetics and safety.First,SH1573 exhibited a strong selective inhibition of mIDH2 R140 Q protein,which could effectively reduce the production of 2-HG in cell lines,serum and tumors of an animal model.It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models.Then,it was confirmed that SH1573 possessed characteristics of high bioavailability,good metabolic stability and wide tissue distribution.Finally,toxicological data showed that SH1573 had no effects on the respiratory system,cardiovascular system and nervous system,and was genetically safe.This research successfully promoted the approval of SH1573 for clinical trials(CTR20200247).All experiments demonstrated that,as a potential drug against mIDH2 R140 Q acute myeloid leukaemia,SH1573 was effective and safe.展开更多
This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s...This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s Hospital were selected for this study from January 2020 to January 2022,and all of the patients were elderly patients with acute myeloid leukemia.Around 23 patients were selected for this study,subsequently the patients were divided into two groups;Group A contained 11 patients and was given decitabine in combination with HAG;and Group B contained 12 patients,and was given azacitidine in combination with HAG.This study showed that the treatment effective rates of patients in both groups were 90.91%and 58.33%,respectively,with a small difference(p>0.05)in the data comparison.The incidence of adverse reactions in the two groups was 63.64%and 16.67%,respectively,with the incidence in group B is significantly(p<0.05)lower compared with group A.Meanwhile,compared with group B,patients in group A had a significantly(p<0.05)shorter mean time to WBC normalization,higher HB and PLT levels,lower WBC levels were lower,all the survival duration times were longer,and subpopulation indicators of peripheral blood T lymphocytes were more in line with normal values.In summary,this study demonstrated that the combination of azacitidine and HAG therapies for the treatment of elderly patients with acute myeloid leukemia is more effective,furthermore can reduce significantly the incidence of adverse treatment effects in patients.展开更多
Acute myeloid leukaemia(AML)is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing.AML cells implement biochemical mechanisms which allow them not only to survive,but also to su...Acute myeloid leukaemia(AML)is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing.AML cells implement biochemical mechanisms which allow them not only to survive,but also to successfully escape immune surveillance.ln this work,we discuss crucial molecular mechanisms used by human AML cells in order to evade immune attack.展开更多
Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Her...Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.展开更多
基金Supported by the National Natural Science Foundation of China,No.81670155.
文摘BACKGROUND The prognosis of paediatric primary refractory/relapsed acute myeloid leukaemia(R/R AML)remains poor.Intensive therapy is typically used as salvage treatment for those with R/R AML.No data are currently available about the use of the CLAG-M protocol as salvage therapy in paediatric patients with R/R AML.CASE SUMMARY An 8-year-old patient was diagnosed with acute myeloid leukaemia by bone marrow morphology and immunophenotype.The patient showed poor response to two cycles of induction therapy with 60%blast cells in the bone marrow after the second induction cycle.The patient achieved complete remission after being treated with the CLAG-M protocol as salvage therapy before undergoing umbilical cord blood stem cell transplantation.Morphological complete remission with haematological recovery has hitherto been maintained over 4 mo.Abnormal gene mutations detected at diagnosis were undetectable after haematopoietic stem cell transplantation.CONCLUSION Here we present a paediatric patient with primary refractory acute myeloid leukaemia who was successfully treated with the CLAG-M protocol.Given the positive results of the presented patient,large-scale clinical studies are required to assess the role of the CLAG-M protocol in the salvage treatment of refractory or relapsed AML in childhood.
基金This study was supported by a grant from NIH (No. CA14599).
文摘The important aim in cancer treatment is the selective killing of cancer cells without damaging healthy cells and the most commonly used chemotherapy for eliminating cancer is achieved by activating the mitochondrial apoptotic pathway. Therefore, identification of new agents that can selectively kill cancer cells becomes crucial in cancer clinical treatment.
基金supported by National Key Research and Development Program of China(No.2017YFA0205200)National Natural Science Foundation of China(Nos.81773766 and 81903845)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20161458,China)the“Double First-Class”University project(No.CPU2018GY38,China)。
文摘Acute myeloid leukaemia(AML) is the most common form of acute leukaemia in adults,with increasing incidence with age and a generally poor prognosis.Almost 20% of AML patients express mutant isocitrate dehydrogenase 2(mIDH2),which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate(2-HG),resulting in poor prognosis.Thus,global institutions have been working to develop mIDH2 inhibitors.SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised.We have conducted a comprehensive study on its pharmacodynamics,pharmacokinetics and safety.First,SH1573 exhibited a strong selective inhibition of mIDH2 R140 Q protein,which could effectively reduce the production of 2-HG in cell lines,serum and tumors of an animal model.It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models.Then,it was confirmed that SH1573 possessed characteristics of high bioavailability,good metabolic stability and wide tissue distribution.Finally,toxicological data showed that SH1573 had no effects on the respiratory system,cardiovascular system and nervous system,and was genetically safe.This research successfully promoted the approval of SH1573 for clinical trials(CTR20200247).All experiments demonstrated that,as a potential drug against mIDH2 R140 Q acute myeloid leukaemia,SH1573 was effective and safe.
文摘This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s Hospital were selected for this study from January 2020 to January 2022,and all of the patients were elderly patients with acute myeloid leukemia.Around 23 patients were selected for this study,subsequently the patients were divided into two groups;Group A contained 11 patients and was given decitabine in combination with HAG;and Group B contained 12 patients,and was given azacitidine in combination with HAG.This study showed that the treatment effective rates of patients in both groups were 90.91%and 58.33%,respectively,with a small difference(p>0.05)in the data comparison.The incidence of adverse reactions in the two groups was 63.64%and 16.67%,respectively,with the incidence in group B is significantly(p<0.05)lower compared with group A.Meanwhile,compared with group B,patients in group A had a significantly(p<0.05)shorter mean time to WBC normalization,higher HB and PLT levels,lower WBC levels were lower,all the survival duration times were longer,and subpopulation indicators of peripheral blood T lymphocytes were more in line with normal values.In summary,this study demonstrated that the combination of azacitidine and HAG therapies for the treatment of elderly patients with acute myeloid leukemia is more effective,furthermore can reduce significantly the incidence of adverse treatment effects in patients.
文摘Acute myeloid leukaemia(AML)is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing.AML cells implement biochemical mechanisms which allow them not only to survive,but also to successfully escape immune surveillance.ln this work,we discuss crucial molecular mechanisms used by human AML cells in order to evade immune attack.
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0107804)the National Natural Science Foundation of China(81900117,82131430173)the CAMS Initiative for Innovative Medicine(2021-I2M-1–040).
文摘Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.