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PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia
[Display omitted] •Mitochondrial DNA (mtDNA) copy number is elevated in pediatric AML patients.•Elevated mtDNA copy number predicts aggressive disease and lower survival outcomes.•MtDNA copy number is possibly driven by PGC1A, likely independent of MYC. Mitochondrial DNA (mtDNA) copy number alterati...
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| Published in: | Mitochondrion 2021-05, Vol.58, p.246-254 |
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| Main Authors: | , , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c356t-6ab91632833e070ece55ecf46991ca70292b5cb58ab7096566303a6b00f6736c3 |
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| cites | cdi_FETCH-LOGICAL-c356t-6ab91632833e070ece55ecf46991ca70292b5cb58ab7096566303a6b00f6736c3 |
| container_end_page | 254 |
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| container_start_page | 246 |
| container_title | Mitochondrion |
| container_volume | 58 |
| creator | Chaudhary, Shilpi Ganguly, Shuvadeep Palanichamy, Jayanth Kumar Singh, Archna Bakhshi, Radhika Jain, Ayushi Chopra, Anita Bakhshi, Sameer |
| description | [Display omitted]
•Mitochondrial DNA (mtDNA) copy number is elevated in pediatric AML patients.•Elevated mtDNA copy number predicts aggressive disease and lower survival outcomes.•MtDNA copy number is possibly driven by PGC1A, likely independent of MYC.
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 |
| doi_str_mv | 10.1016/j.mito.2021.03.013 |
| format | article |
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•Mitochondrial DNA (mtDNA) copy number is elevated in pediatric AML patients.•Elevated mtDNA copy number predicts aggressive disease and lower survival outcomes.•MtDNA copy number is possibly driven by PGC1A, likely independent of MYC.
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.</description><identifier>ISSN: 1567-7249</identifier><identifier>EISSN: 1872-8278</identifier><identifier>DOI: 10.1016/j.mito.2021.03.013</identifier><identifier>PMID: 33812061</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Acute myeloid leukemia ; Biogenesis ; Child ; DNA Copy Number Variations ; DNA, Mitochondrial - genetics ; Humans ; Leukemia, Myeloid, Acute - genetics ; Mitochondrial DNA copy number ; MYC ; Outcome Assessment, Health Care ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics ; PGC1A</subject><ispartof>Mitochondrion, 2021-05, Vol.58, p.246-254</ispartof><rights>2021 Elsevier B.V. and Mitochondria Research Society</rights><rights>Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-6ab91632833e070ece55ecf46991ca70292b5cb58ab7096566303a6b00f6736c3</citedby><cites>FETCH-LOGICAL-c356t-6ab91632833e070ece55ecf46991ca70292b5cb58ab7096566303a6b00f6736c3</cites><orcidid>0000-0002-7296-6088 ; 0000-0001-6487-6632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33812061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chaudhary, Shilpi</creatorcontrib><creatorcontrib>Ganguly, Shuvadeep</creatorcontrib><creatorcontrib>Palanichamy, Jayanth Kumar</creatorcontrib><creatorcontrib>Singh, Archna</creatorcontrib><creatorcontrib>Bakhshi, Radhika</creatorcontrib><creatorcontrib>Jain, Ayushi</creatorcontrib><creatorcontrib>Chopra, Anita</creatorcontrib><creatorcontrib>Bakhshi, Sameer</creatorcontrib><title>PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia</title><title>Mitochondrion</title><addtitle>Mitochondrion</addtitle><description>[Display omitted]
•Mitochondrial DNA (mtDNA) copy number is elevated in pediatric AML patients.•Elevated mtDNA copy number predicts aggressive disease and lower survival outcomes.•MtDNA copy number is possibly driven by PGC1A, likely independent of MYC.
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.</description><subject>Acute myeloid leukemia</subject><subject>Biogenesis</subject><subject>Child</subject><subject>DNA Copy Number Variations</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Humans</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Mitochondrial DNA copy number</subject><subject>MYC</subject><subject>Outcome Assessment, Health Care</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics</subject><subject>PGC1A</subject><issn>1567-7249</issn><issn>1872-8278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kMFu1DAQhi3UipbCC3BAPvaSMLYbO5G4rBYoSFXbA5wtZzKr9ZLEwU4q7dvjaEuPPc1o9P2_NB9jHwWUAoT-fCgHP4dSghQlqBKEesMuRW1kUUtTn-W90qYw8qa5YO9SOgAII6R8yy6UqoUELS7Z_vF2Kza8i_6JRk7j3o1IHV-LcR_GfHc9_3q_4RimIx-XoaXIp0idxznxsMwYBuJ-5FM-uTl65A6XmfhwpD74jve0_KHBu_fsfOf6RB-e5xX7_f3br-2P4u7h9ud2c1egqvRcaNc2QitZK0VggJCqinB3o5tGoDMgG9lW2Fa1aw00utJagXK6BdhpozSqK3Z96p1i-LtQmu3gE1Lfu5HCkqysoM5atK4zKk8oxpBSpJ2doh9cPFoBdjVsD3YVYVfDFpTNhnPo03P_0g7UvUT-K83AlxNA-csnT9Em9LRa9ZFwtl3wr_X_Az0ejI4</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Chaudhary, Shilpi</creator><creator>Ganguly, Shuvadeep</creator><creator>Palanichamy, Jayanth Kumar</creator><creator>Singh, Archna</creator><creator>Bakhshi, Radhika</creator><creator>Jain, Ayushi</creator><creator>Chopra, Anita</creator><creator>Bakhshi, Sameer</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7296-6088</orcidid><orcidid>https://orcid.org/0000-0001-6487-6632</orcidid></search><sort><creationdate>202105</creationdate><title>PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia</title><author>Chaudhary, Shilpi ; Ganguly, Shuvadeep ; Palanichamy, Jayanth Kumar ; Singh, Archna ; Bakhshi, Radhika ; Jain, Ayushi ; Chopra, Anita ; Bakhshi, Sameer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-6ab91632833e070ece55ecf46991ca70292b5cb58ab7096566303a6b00f6736c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute myeloid leukemia</topic><topic>Biogenesis</topic><topic>Child</topic><topic>DNA Copy Number Variations</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Humans</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Mitochondrial DNA copy number</topic><topic>MYC</topic><topic>Outcome Assessment, Health Care</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics</topic><topic>PGC1A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chaudhary, Shilpi</creatorcontrib><creatorcontrib>Ganguly, Shuvadeep</creatorcontrib><creatorcontrib>Palanichamy, Jayanth Kumar</creatorcontrib><creatorcontrib>Singh, Archna</creatorcontrib><creatorcontrib>Bakhshi, Radhika</creatorcontrib><creatorcontrib>Jain, Ayushi</creatorcontrib><creatorcontrib>Chopra, Anita</creatorcontrib><creatorcontrib>Bakhshi, Sameer</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Mitochondrion</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chaudhary, Shilpi</au><au>Ganguly, Shuvadeep</au><au>Palanichamy, Jayanth Kumar</au><au>Singh, Archna</au><au>Bakhshi, Radhika</au><au>Jain, Ayushi</au><au>Chopra, Anita</au><au>Bakhshi, Sameer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia</atitle><jtitle>Mitochondrion</jtitle><addtitle>Mitochondrion</addtitle><date>2021-05</date><risdate>2021</risdate><volume>58</volume><spage>246</spage><epage>254</epage><pages>246-254</pages><issn>1567-7249</issn><eissn>1872-8278</eissn><abstract>[Display omitted]
•Mitochondrial DNA (mtDNA) copy number is elevated in pediatric AML patients.•Elevated mtDNA copy number predicts aggressive disease and lower survival outcomes.•MtDNA copy number is possibly driven by PGC1A, likely independent of MYC.
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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33812061</pmid><doi>10.1016/j.mito.2021.03.013</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7296-6088</orcidid><orcidid>https://orcid.org/0000-0001-6487-6632</orcidid></addata></record> |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Acute myeloid leukemia Biogenesis Child DNA Copy Number Variations DNA, Mitochondrial - genetics Humans Leukemia, Myeloid, Acute - genetics Mitochondrial DNA copy number MYC Outcome Assessment, Health Care Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics PGC1A |
| title | PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia |
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