RESUMO
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.
RESUMO
The Serra Spanish mackerel, Scomberomorus brasiliensis, is one of the most important fishery resources in the western tropical Atlantic, including northern and eastern Brazil. Despite its economic importance, few genetic markers have been sequenced in this species, and little is known of its population genetics. The present study evaluated the genetic variability of 110 individuals, representing three distinct Brazilian populations (Macapá, Fortaleza and Paranaguá), based on a segment of the mitochondrial Control Region. The sequences revealed high levels of genetic diversity, and suggested marked connectivity among the studied populations. A variable repeat was also found in the 3' portion of the studied Control Region fragment, which may prove useful as a marker in future genetic population studies of S. brasiliensis.
