BACKGROUND: The mechanisms responsible for resistant or recurrent disease in childhood
non-Hodgkin lymphoma (NHL) are not yet fully understood. A unique mechanism suggesting the role of the mitochondria as the key energy source responsible for residual cells has been assessed in the clinical setting on specimens from patients on
therapy were found to have increased copies of
mitochondrial DNA (
mtDNA) associated with positive
minimal residual disease and/or persistent disease (MRD/PD) status. The potential role of
mtDNA in MRD/PD emphasizes queries into the contributions of relevant enzymatic pathways responsible for MRD/PD. This study hypothesized that in an in-vitro model, recovering or residual cells from chemotoxicity will exhibit an increase in both
citrate synthase and
isocitrate dehydrogenase expression and decrease in
succinate dehydrogenase expression. PROCEDURE: Ramos cells (
Burkitt lymphoma cell line) were exposed to varying concentrations of
doxorubicin and
vincristine for 1 hr; and allowing for recovery in culture over a 7-day period.
cDNA was extracted on days 1 and 7 of the cell culture period to assess the relative expression of the aforementioned genes. RESULTS: Increase
citrate synthase, increase
isocitrate dehydrogenase and decrease
succinate dehydrogenase expressions were found in recovering Ramos cells. CONCLUSION: Recovering
lymphoma cells appear to compensate by regulating enzymatic levels of appropriate genes in the Krebs Cycle suggesting an important role of the mitochondria in the presence of residual cells.