由PGC1A驱动的线粒体DNA拷贝数增加可预测儿童急性髓系白血病的预后。
PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia.
作者信息
Chaudhary Shilpi, Ganguly Shuvadeep, Palanichamy Jayanth Kumar, Singh Archna, Bakhshi Radhika, Jain Ayushi, Chopra Anita, Bakhshi Sameer
机构信息
Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
出版信息
Mitochondrion. 2021 May;58:246-254. doi: 10.1016/j.mito.2021.03.013. Epub 2021 Apr 1.
Mitochondrial DNA (mtDNA) copy number alterations occur in acute myeloid leukemia (AML). We evaluated regulation and biological significance of mtDNA copy number in pediatric AML patients (n = 123) by qRT-PCR, and in-vitro studies. MtDNA copy number was significantly higher (p < 0.001) and an independent predictor of aggressive disease (p = 0.006), lower event free survival (p = 0.033), and overall survival (p = 0.007). Expression of TFAM, POLG, POLRMT, MYC and ND3 were significantly upregulated. In cell lines, PGC1A inhibition decreased mtDNA copy number while MYC inhibition had no effect. PGC1A may contribute to enhanced mtDNA copy number, which predicts disease aggressiveness and inferior survival outcome.
线粒体DNA（mtDNA）拷贝数改变在急性髓系白血病（AML）中会出现。我们通过定量逆转录聚合酶链反应（qRT-PCR）以及体外研究，评估了小儿AML患者（n = 123）中mtDNA拷贝数的调控及其生物学意义。mtDNA拷贝数显著更高（p < 0.001），并且是侵袭性疾病的独立预测因子（p = 0.006），无事件生存期较低（p = 0.033），总生存期也较低（p = 0.007）。线粒体转录因子A（TFAM）、聚合酶γ（POLG）、线粒体RNA聚合酶（POLRMT）、原癌基因MYC和烟酰胺腺嘌呤二核苷酸脱氢酶亚基3（ND3）的表达显著上调。在细胞系中，过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1A）的抑制降低了mtDNA拷贝数，而MYC的抑制则没有效果。PGC1A可能有助于增加mtDNA拷贝数，这预示着疾病的侵袭性和较差的生存结果。
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