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
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.
