PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia

被引：21

作者：

Chaudhary, Shilpi ^{[1
]}

Ganguly, Shuvadeep ^{[1
]}

Palanichamy, Jayanth Kumar ^{[2
]}

Singh, Archna ^{[2
]}

Bakhshi, Radhika ^{[3
]}

Jain, Ayushi ^{[2
]}

Chopra, Anita ^{[4
]}

Bakhshi, Sameer ^{[1
]}

机构：

[1] All India Inst Med Sci, Dr BRA Inst Rotary Canc Hosp, Dept Med Oncol, New Delhi 110029, India

[2] All India Inst Med Sci, Dept Biochem, New Delhi, India

[3] Univ Delhi, Shaheed Rajguru Coll Appl Sci Women, Delhi, India

[4] All India Inst Med Sci, Dr BRA Inst Rotary Canc Hosp, Dept Lab Oncol, New Delhi, India

来源：

MITOCHONDRION | 2021年 / 58卷

关键词：

Acute myeloid leukemia; Mitochondrial DNA copy number; PGC1A; MYC; Child; Biogenesis; C-MYC; BIOGENESIS; GENES; AML; CARCINOGENESIS; TRANSLATION; RESISTANCE; CAPACITY; TARGET; CELLS;

D O I：

10.1016/j.mito.2021.03.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：246 / 254

页数：9

共 40 条

[1] Alterations of Mitochondria and Related Metabolic Pathways in Leukemia: A Narrative Review [J].

Al Ageeli, Essam .

SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES, 2020, 8 (01) :3-11

[2] Targeting mitochondrial RNA polymerase in acute myeloid leukemia [J].

Bralha, Fernando N. ;

Liyanage, Sanduni U. ;

Hurren, Rose ;

Wang, Xiaoming ;

Son, Meong Hi ;

Fung, Thomas A. ;

Chingcuanco, Francine B. ;

Tung, Aveline Y. W. ;

Andreazza, Ana C. ;

Psarianos, Pamela ;

Schimmer, Aaron D. ;

Salmena, Leonardo ;

Laposa, Rebecca R. .

ONCOTARGET, 2015, 6 (35) :37216-37228

[3] Altered Mitochondrial Signalling and Metabolism in Cancer [J].

Chattopadhyay, Esita ;

Roy, Bidyut .

FRONTIERS IN ONCOLOGY, 2017, 7

[4] Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias [J].

Chaudhury, Shahzya ;

O'Connor, Caitriona ;

Canete, Ana ;

Bittencourt-Silvestre, Joana ;

Sarrou, Evgenia ;

Prendergast, Aine ;

Choi, Jarny ;

Johnston, Pamela ;

Wells, Christine A. ;

Gibson, Brenda ;

Keeshan, Karen .

NATURE COMMUNICATIONS, 2018, 9

[5] The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas [J].

D'Andrea, Aleco ;

Gritti, Ilaria ;

Nicoli, Paola ;

Giorgio, Marco ;

Doni, Mirko ;

Conti, Annalisa ;

Bianchi, Valerio ;

Casoli, Lucia ;

Sabo, Arianna ;

Mironov, Alexandre ;

Beznoussenko, Galina V. ;

Amati, Bruno .

ONCOTARGET, 2016, 7 (45) :72415-72430

[6] Therapeutic Targeting of Myc-Reprogrammed Cancer Cell Metabolism [J].

Dang, C. V. .

METABOLISM AND DISEASE, 2011, 76 :369-374

[7] Mitochondrial DNA repair in aging and disease [J].

Druzhyna, Nadiya M. ;

Wilson, Glenn L. ;

LeDoux, Susan P. .

MECHANISMS OF AGEING AND DEVELOPMENT, 2008, 129 (7-8) :383-390

[8] Akt and c-Myc Differentially Activate Cellular Metabolic Programs and Prime Cells to Bioenergetic Inhibition [J].

Fan, Yongjun ;

Dickman, Kathleen G. ;

Zong, Wei-Xing .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (10) :7324-7333

[9] Mitochondrial Structure, Function and Dynamics Are Temporally Controlled by c-Myc [J].

Graves, J. Anthony ;

Wang, Yudong ;

Sims-Lucas, Sunder ;

Cherok, Edward ;

Rothermund, Kristi ;

Branca, Maria F. ;

Elster, Jennifer ;

Beer-Stolz, Donna ;

Van Houten, Bennett ;

Vockley, Jerry ;

Prochownik, Edward V. .

PLOS ONE, 2012, 7 (05)

[10] Mitochondrial DNA and carcinogenesis (Review) [J].

Grzybowska-Szatkowska, Ludmila ;

Slaska, Brygida .

MOLECULAR MEDICINE REPORTS, 2012, 6 (05) :923-930

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