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

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.

• Authors: Júlia Plentz Portich, Rafael Pereira Dos Santos, Nathalia Kersting, Karolina Brochado Jorge, Pietro Rebelo Casagrande, Gabriela Dos Santos Costa, Jéssica Maria Gonçalves Dias Cionek, Danielly Brufatto Olguins, Marialva Sinigaglia, Franciele Faccio Busatto, Jenifer Saffi, Sharbel Weidner Maluf, Jiseh Fagundes Loss, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias
• Journal: Leukemia research (Leuk Res) Vol. 54 Pg. 59-65 (03 2017) ISSN: 1873-5835 [Electronic] England
• PMID: 28109975 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Topics

• Adolescent
• Bone Marrow (pathology)
• Child
• Comet Assay
• DNA Damage (drug effects)
• DNA Repair
• Female
• Follow-Up Studies
• Humans
• Induction Chemotherapy (adverse effects)
• Infant
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics)
• Prognosis
• Time Factors