학술논문
PARP1 Characterization as a Potential Biomarker for BCR::ABL1 p190+ Acute Lymphoblastic Leukemia
Document Type
article
Author
Caio Bezerra Machado; Emerson Lucena da Silva; Wallax Augusto Silva Ferreira; Flávia Melo Cunha de Pinho Pessoa; Andreza Urba de Quadros; Daianne Maciely Carvalho Fantacini; Izadora Peter Furtado; Rafaela Rossetti; Roberta Maraninchi Silveira; Sarah Caroline Gomes de Lima; Fernando Augusto Rodrigues Mello Júnior; Aline Damasceno Seabra; Edith Cibelle de Oliveira Moreira; Manoel Odorico de Moraes Filho; Maria Elisabete Amaral de Moraes; Raquel Carvalho Montenegro; Rodrigo Monteiro Ribeiro; André Salim Khayat; Rommel Mário Rodriguez Burbano; Edivaldo Herculano Correa de Oliveira; Dimas Tadeu Covas; Lucas Eduardo Botelho de Souza; Caroline de Fátima Aquino Moreira-Nunes
Source
Cancers, Vol 15, Iss 23, p 5510 (2023)
Subject
Language
English
ISSN
2072-6694
Abstract
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.