Pediatric blood & cancer · 2008
Chemotoxicity recovery of mitochondria in non-Hodgkin lymphoma resulting in minimal residual disease.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kusao Ian, Agsalda Melissa, Troelstrup David, Villanueva Nicolas, Shiramizu Bruce
Аннотация
BACKGROUND: The mechanisms responsible for resistant disease or recurrence of non-Hodgkin 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.
PROCEDURE: 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-time polymerase chain reaction (PCR).
RESULTS: Increased mtDNA copy numbers were found in clinical specimens with MRD/PD as well as in recovering Ramos cells from chemotoxicity.
CONCLUSIONS: 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.
PROCEDURE: 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-time polymerase chain reaction (PCR).
RESULTS: Increased mtDNA copy numbers were found in clinical specimens with MRD/PD as well as in recovering Ramos cells from chemotoxicity.
CONCLUSIONS: 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.