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Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
DNA damage response in patients with pediatric Acute Lymphoid Leukemia during induction therapy
Júlia Plentz Portich1, Rafael Pereira Dos Santos2, Nathalia Kersting1
1Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract:
Predicting the individual response to chemotherapy is a crucial challenge in cancer treatment. DNA damage caused by antitumor therapies evokes different repair mechanisms responses, such as Nucleotide Excision Repair (NER), whose components are being studied as prognosis biomarkers and target therapies. However, few reports have addressed DNA damages in pediatric Acute Lymphoid Leukemia (ALL). Hence, we conducted an observational follow-up study with pediatric patients to assess DNA damage (by Comet Assay) and gene expression from NER pathway during chemotherapy induction. Bone marrow samples from diagnosis, 15th(D15) and 35th (D35) days of the treatment were collected from 28 patients with ALL. There was no increase in damage index. However, there was a reduction of cells with low damages on D35 compared with diagnosis. NER pathway expression remained the same, however, in a single patient, a significant decrease was observed, maybe due to silencing or downregulation of repair pathways. DNA damage levels and repair may influence the clinical outcome, being involved in drug resistance and risk of relapse. In pediatric ALL, we analyzed for the first time DNA damage and repair behavior in BM samples. Monitoring patient's outcomes will help to access the implication of our findings in survival and relapse rates.
Insights
This study examined DNA damage and repair in pediatric Acute Lymphoid Leukemia (ALL) patients undergoing chemotherapy. While overall DNA damage didn't increase, changes in low-damage cells suggest repair mechanisms may influence treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Predicting chemotherapy response is vital in cancer treatment.
- Nucleotide Excision Repair (NER) pathways are implicated in DNA repair and cancer prognosis.
- Limited research exists on DNA damage and repair in pediatric Acute Lymphoid Leukemia (ALL).
Purpose of the Study:
- To investigate DNA damage and NER pathway gene expression in pediatric ALL patients during chemotherapy induction.
- To explore the potential link between DNA damage, repair mechanisms, and clinical outcomes in pediatric ALL.
Main Methods:
- An observational follow-up study involving 28 pediatric ALL patients.
- Bone marrow samples collected at diagnosis, day 15 (D15), and day 35 (D35) of treatment.
- Assessed DNA damage using the Comet Assay and analyzed NER pathway gene expression.
Main Results:
- No significant increase in the overall DNA damage index was observed.
- A reduction in cells with low DNA damage was noted by D35 compared to diagnosis.
- NER pathway gene expression remained stable, with one patient showing a significant decrease, possibly due to pathway downregulation.
Conclusions:
- DNA damage and repair dynamics in pediatric ALL bone marrow samples were analyzed for the first time.
- Observed changes in DNA damage and repair may influence drug resistance and relapse risk.
- Further monitoring of patient outcomes is needed to determine the implications for survival and relapse rates.
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