PARP1 Characterization as a Potential Biomarker for BCR::ABL1 p190+ Acute Lymphoblastic Leukemia.

Autor: Machado CB; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., da Silva EL; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., Ferreira WAS; Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SAMAM), Evandro Chagas Institute (IEC), Ananindeua 67030-000, PA, Brazil., Pessoa FMCP; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., de Quadros AU; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Fantacini DMC; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Furtado IP; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Rossetti R; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Silveira RM; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., de Lima SCG; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Mello Júnior FAR; Molecular Biology Laboratory, Ophir Loyola Hospital, Belém 66063-240, PA, Brazil., Seabra AD; Molecular Biology Laboratory, Ophir Loyola Hospital, Belém 66063-240, PA, Brazil., Moreira ECO; Institute of Health and Biological Studies, Federal University of the South and Southeast of Pará, Marabá 68501-970, PA, Brazil., de Moraes Filho MO; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., de Moraes MEA; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., Montenegro RC; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil., Ribeiro RM; Department of Hematology, Fortaleza General Hospital (HGF), Fortaleza 60150-160, CE, Brazil., Khayat AS; Department of Biological Sciences, Oncology Research Center, Federal University of Pará, Belém 66073-005, PA, Brazil., Burbano RMR; Molecular Biology Laboratory, Ophir Loyola Hospital, Belém 66063-240, PA, Brazil.; Department of Biological Sciences, Oncology Research Center, Federal University of Pará, Belém 66073-005, PA, Brazil., de Oliveira EHC; Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SAMAM), Evandro Chagas Institute (IEC), Ananindeua 67030-000, PA, Brazil., Covas DT; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., de Souza LEB; Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil., Moreira-Nunes CFA; Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil.; Department of Biological Sciences, Oncology Research Center, Federal University of Pará, Belém 66073-005, PA, Brazil.; Northeast Biotechnology Network (RENORBIO), Itaperi Campus, Ceará State University, Fortaleza 60740-903, CE, Brazil.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Nov 22; Vol. 15 (23). Date of Electronic Publication: 2023 Nov 22.
DOI: 10.3390/cancers15235510
Abstrakt: Detection of t(9;22), and consequent BCR::ABL1 fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets. Overall, we demonstrate the effectiveness of PARPi in the treatment of BCR::ABL1 p190+ ALL cell models and that PARP1 is differentially expressed in patient samples. We hope our findings help expand the characterization of molecular profiles in ALL settings and guide future investigations into novel biomarker detection and pharmacological choices in clinical practice.
Databáze: MEDLINE
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