Mitochondrial DNA in residual leukemia cells in cerebrospinal fluid in children with acute lymphoblastic leukemia
Kathryn Egan1, Ian Kusao, David Troelstrup
1Department of Child & Adolescent Psychiatry, Tripler Army Medical Center, Hawaii, USA.
Unlabelled:
This feasibility study was designed to assess the ability to measure mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) cells that contributed to minimal disease/persistent or residual disease (MD/PRD) from children with acute lymphoblastic leukemia (ALL). Increase in mtDNA copies in cancer cells has been suggested to play a role in MD/PRD. CSF as well as blood specimens from 6 children were assayed for MD/PRD and mtDNA copy numbers by quantitative real-time polymerase chain reaction. Of 7 MD/PRD-positive specimens, 6 had increased mtDNA copy numbers; while 11 MD/PRD-negative specimens had no increase in mtDNA copy numbers, p < 0.003. This is the first proof-of-concept study to measure mtDNA copy numbers in MD/PRD-positive CSF specimens from children with ALL. Increase of mtDNA copy numbers in MD/PRD childhood ALL cells and its significance as a mechanism for recurrence requires further investigation.
Keywords:
Minimal residual disease; Acute lymphoblastic leukemia; Central nervous system; Cerebrospinal fluid; Mitochondria.
Insights
Measuring mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) cells of children with acute lymphoblastic leukemia (ALL) may help detect minimal residual disease (MRD). Increased mtDNA copy numbers were found in MRD-positive CSF specimens.
Area of Science:
- Oncology
- Genetics
- Pediatrics
Background:
- Minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a critical prognostic factor.
- Mitochondrial DNA (mtDNA) copy number alterations are implicated in cancer development and progression.
- The central nervous system (CNS) is a common sanctuary site for ALL relapse, making CSF analysis crucial.
Purpose of the Study:
- To assess the feasibility of measuring mtDNA copy numbers in cerebrospinal fluid (CSF) cells from pediatric ALL patients.
- To investigate the correlation between mtDNA copy numbers and minimal/persistent or residual disease (MD/PRD) status in the CNS.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA copy numbers.
- CSF and blood specimens were collected from 6 children diagnosed with ALL.
- Specimens were analyzed for the presence of MD/PRD and corresponding mtDNA levels.
Main Results:
- A significant increase in mtDNA copy numbers was observed in 6 out of 7 MD/PRD-positive CSF specimens (p < 0.003).
- No increase in mtDNA copy numbers was detected in 11 MD/PRD-negative specimens.
- This study represents the first proof-of-concept for measuring mtDNA in MD/PRD-positive CSF cells in childhood ALL.
Conclusions:
- Measuring mtDNA copy numbers in CSF cells is a feasible approach for detecting MD/PRD in pediatric ALL.
- Elevated mtDNA copy numbers in MD/PRD-positive cells suggest a potential role in ALL recurrence.
- Further research is warranted to elucidate the mechanism and clinical significance of increased mtDNA in childhood ALL relapse.
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