Metabolic reprogramming is a hallmark of cancer,with acute myeloid leukemia(AML)being no exception.Mitochondrial function,particularly its role in protecting tumor cells against chemotherapy,is of significant interest...Metabolic reprogramming is a hallmark of cancer,with acute myeloid leukemia(AML)being no exception.Mitochondrial function,particularly its role in protecting tumor cells against chemotherapy,is of significant interest in AML chemoresistance.In this study,we identified mitochondrial DNA content(mtDNAc),measured by quantitative PCR,as a simple and precise marker to stratify the metabolic states of AML patients.We show that patients with high mtDNAc are associated with increased mitochondrial metabolism and a higher dependency on oxidative phosphorylation(OXPHOS),often correlating with chemoresistance.Clinically,patients receiving cytarabine and an anthracycline-based regimen(7+3 regimen)experienced inferior relapse-free survival and a higher overall rate of leukemia recurrence.展开更多
Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia （AML） and discuss the role of emerging novel agents that might be applied in future clinical trials.Data sou...Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia （AML） and discuss the role of emerging novel agents that might be applied in future clinical trials.Data sources The data in this article were collected from PubMed database with relevant English articles published from 1991 to 2009.Study selection Articles regarding the risk stratification and therapeutic options of AML, as well as the characteristics of leukemic stem cells were selected.Results AML is a heterogeneous disease with variable clinical outcome dependent on several prognostic factors,including age, cytogenetics and molecular markers. The advances in the understanding of AML pathogenesis and development will generate potential novel agents that might improve the treatment results of standard chemotherapy.Conclusion Deeper insight into the multiple transforming events of AML may aid us in designing combinations of small molecule inhibitors based on the individual patient characteristics.展开更多
基金supported by Fundação de AmparoàPesquisa do Estado de São Paulo(FAPESP,Grant#2013/08135-2,CNPq:465539/2014-9)D.A.P-M.Received a fellowship from FAPESP(Grant#2017/23117-1)+2 种基金I.W.received a fellowship from FAPESP(Grant#2015/09228-0)L.Q.and P.C.were funded by UKRI/MRC grant#MR/R007608/1.A.R.L-A.Received a research grant and fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Grant#303479/2018-3,#405918/2022-4)I.W and D.A.P-M were sponsored by the Abel Tasman Talent Program(ATTP)of the Graduate School of Medical Sciences of the University of Groningen/University Medical Center Groningen(UG/UMCG),The Netherlands.
文摘Metabolic reprogramming is a hallmark of cancer,with acute myeloid leukemia(AML)being no exception.Mitochondrial function,particularly its role in protecting tumor cells against chemotherapy,is of significant interest in AML chemoresistance.In this study,we identified mitochondrial DNA content(mtDNAc),measured by quantitative PCR,as a simple and precise marker to stratify the metabolic states of AML patients.We show that patients with high mtDNAc are associated with increased mitochondrial metabolism and a higher dependency on oxidative phosphorylation(OXPHOS),often correlating with chemoresistance.Clinically,patients receiving cytarabine and an anthracycline-based regimen(7+3 regimen)experienced inferior relapse-free survival and a higher overall rate of leukemia recurrence.
文摘Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia （AML） and discuss the role of emerging novel agents that might be applied in future clinical trials.Data sources The data in this article were collected from PubMed database with relevant English articles published from 1991 to 2009.Study selection Articles regarding the risk stratification and therapeutic options of AML, as well as the characteristics of leukemic stem cells were selected.Results AML is a heterogeneous disease with variable clinical outcome dependent on several prognostic factors,including age, cytogenetics and molecular markers. The advances in the understanding of AML pathogenesis and development will generate potential novel agents that might improve the treatment results of standard chemotherapy.Conclusion Deeper insight into the multiple transforming events of AML may aid us in designing combinations of small molecule inhibitors based on the individual patient characteristics.
