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Leuk Res. 2017 Mar;54:59-65. doi: 10.1016/j.leukres.2017.01.013. Epub 2017 Jan 11.

DNA damage response in patients with pediatric Acute Lymphoid Leukemia during induction therapy.

Author information

1
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
2
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Children's Cancer Institute, Porto Alegre, RS, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics (PPGFT), Federal University of Rio Grande do Sul UFRGS, Porto Alegre, RS, Brazil.
3
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Children's Cancer Institute, Porto Alegre, RS, Brazil.
4
Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, UFCSPA, Porto Alegre, RS, Brazil.
5
Federal University of Santa Catarina, UFSC, Florianópolis, SC, Brazil.
6
Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
7
Children's Cancer Institute, Porto Alegre, RS, Brazil.
8
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics (PPGFT), Federal University of Rio Grande do Sul UFRGS, Porto Alegre, RS, Brazil.
9
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Children's Cancer Institute, Porto Alegre, RS, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics (PPGFT), Federal University of Rio Grande do Sul UFRGS, Porto Alegre, RS, Brazil. Electronic address: labpesquisa@ici-rs.org.br.

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.

KEYWORDS:

Acute Lymphoid Leukemia; Comet assay; DNA damage; DNA repair; NER pathway

PMID:
28109975
DOI:
10.1016/j.leukres.2017.01.013
[Indexed for MEDLINE]

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