{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T15:54:56Z","timestamp":1768924496029,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,3,5]],"date-time":"2008-03-05T00:00:00Z","timestamp":1204675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanisms responsible for resistant disease or recurrence of non\u2010Hodgkin lymphoma (NHL) in children cover a wide spectrum from drug resistance to genetic mutations. A unique mechanism suggesting the role of mitochondria as the key energy source is studied following a clinical observation where pediatric Burkitt lymphoma (BL) specimens from patients on therapy were found to have increased copies of mitochondria DNA (mtDNA) in specimens which were shown to be positive for minimal residual disease and\/or persistent disease (MRD\/PD). This study hypothesized that the mitochondria play an important role in a cell's recovery from toxicity via a compensatory increase in mtDNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>BL specimens with MRD\/PD were assayed for mtDNA. An in vitro model was then designed using Ramos cell lines by exposing the lymphoma cells to varying concentrations of doxorubicin and vincristine for 1 hr; and allowing for recovery in culture over 7 days. DNA was extracted from aliquots over several days to determine mtDNA copy numbers by real\u2010time polymerase chain reaction (PCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased mtDNA copy numbers were found in clinical specimens with MRD\/PD as well as in recovering Ramos cells from chemotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The recovering lymphoma cells from the chemotoxic effects appeared to compensate by increasing mtDNA content, which may contribute to the clinical residual or resistant disease in some cases of childhood BL. Pediatr Blood Cancer 2008;51:193\u2013197. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.21545","type":"journal-article","created":{"date-parts":[[2008,3,5]],"date-time":"2008-03-05T16:16:23Z","timestamp":1204733783000},"page":"193-197","source":"Crossref","is-referenced-by-count":10,"title":["Chemotoxicity recovery of mitochondria in non\u2010Hodgkin lymphoma resulting in minimal residual disease"],"prefix":"10.1002","volume":"51","author":[{"given":"Ian","family":"Kusao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Agsalda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Troelstrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Villanueva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Shiramizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,3,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-0119"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21110"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.04.015"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0734"},{"key":"e_1_2_6_6_2","first-page":"398","article-title":"Changes in copy number and deletion development of mitochondrial DNA in blood cells from breast cancer patients during radiochemotherapy","volume":"52","author":"Malakhova LV","year":"2006","journal-title":"Vopr Onkol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403043"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/mi.5.2.7"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.09.010"},{"key":"e_1_2_6_10_2","first-page":"332","article-title":"Classification, staging and end results of treatment of childhood non\u2010Hodgkin's lymphomas: Dissimilarities from lymphomas in adults","volume":"7","author":"Murphy SB","year":"1980","journal-title":"Semin Oncol"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401559"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04134.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200302000-00005"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.5.1797.005k30_1797_1803"},{"key":"e_1_2_6_15_2","doi-asserted-by":"crossref","first-page":"M83","DOI":"10.1177\/135965350501002S09","article-title":"Mitochondrial DNA levels of peripheral blood mononuclear cells and subcutaneous adipose tissue from thigh, fat and abdomen of HIV\u20101 seropositive and negative individuals","volume":"10","author":"Gerschenson M","year":"2005","journal-title":"Antivir Ther"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(02)00026-9"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(03)00098-5"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.09.017"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-068478"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209607"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210681"},{"key":"e_1_2_6_22_2","first-page":"1339","article-title":"Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species","volume":"21","author":"Groninger E","year":"2002","journal-title":"Int J Oncol"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.2174\/138955707782110196"},{"key":"e_1_2_6_24_2","first-page":"55","article-title":"Increase in mitochondrial DNA quantity and impairment of oxidative phosphorylation in bovine fibroblast cells treated with ethidium bromide for 15 passages in culture","volume":"5","author":"Chiaratti MR","year":"2006","journal-title":"Genet Mol Res"},{"key":"e_1_2_6_25_2","first-page":"721","article-title":"The increase in mitochondrial DNA copy number in the tissues of gamma\u2010irradiated mice","volume":"10","author":"Malakhova L","year":"2005","journal-title":"Cell Mol Biol Lett"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01063-K"}],"container-title":["Pediatric Blood &amp; 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