Targeting aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia

• Published in: Scientific reports 2020-12, Vol.10 (1), p.21272, Article 21272
• Main Authors: Moreira-Nunes, Caroline Aquino, Mesquita, Felipe Pantoja, Portilho, Adrhyann Jullyanne de Sousa, Mello Júnior, Fernando Augusto Rodrigues, Maués, Jersey Heitor da Silva, Pantoja, Laudreísa da Costa, Wanderley, Alayde Vieira, Khayat, André Salim, Zuercher, William J., Montenegro, Raquel Carvalho, de Moraes-Filho, Manoel Odorico, de Moraes, Maria Elisabete Amaral
• Format: Article
• Language: English
• Subjects: 631/208; 631/208/199; 631/208/68; 631/337; 631/67; 631/67/1990; 631/80; Acute lymphoblastic leukemia; Apoptosis; Aurora Kinase A - metabolism; Aurora Kinase B - metabolism; Biomarkers; Biomarkers, Tumor - metabolism; Brazil - epidemiology; Case-Control Studies; Caspase; Cell activation; Cell cycle; Cell death; Child; Child, Preschool; Cytogenetics; Female; Fusion Proteins, bcr-abl - metabolism; Gene expression; Humanities and Social Sciences; Humans; Infant; K562 Cells; Kinases; Leukemia; Leukocytes; Male; Medical prognosis; multidisciplinary; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - enzymology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Prognosis; Protein Interaction Maps; Science; Science (multidisciplinary); Survival
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-78024-8

Aurora kinases (AURKA and AURKB) are mitotic kinases with an important role in the regulation of several mitotic events, and in hematological malignancies, AURKA and AURKB hyperexpression are found in patients with cytogenetic abnormalities presenting a unfavorable prognosis. The aim of this study was evaluated the mRNA expression profile of pediatric Acute Lymphoblastic Leukaemia (ALL) patients and the efficacy of two AURKA and AURKB designed inhibitors (GW809897X and GW806742X) in a leukemia cell line as a potential novel therapy for ALL patients. Cellular experiments demonstrated that both inhibitors induced cell death with caspase activation and cell cycle arrest, however only the GW806742X inhibitor decreased with more efficacy AURKA and AURKB expression in K-562 leukemia cells. In ALL patients both AURKA and AURKB showed a significant overexpression, when compared to health controls. Moreover, AURKB expression level was significant higher than AURKA in patients, and predicted a poorer prognosis with significantly lower survival rates. No differences were found in AURKA and AURKB expression between gene fusions, immunophenotypic groups, white blood cells count, gender or age. In summary, the results in this study indicates that the AURKA and AURKB overexpression are important findings in pediatric ALL, and designed inhibitor, GW806742X tested in vitro were able to effectively inhibit the gene expression of both aurora kinases and induce apoptosis in K-562 cells, however our data clearly shown that AURKB proves to be a singular finding and potential prognostic biomarker that may be used as a promising therapeutic target to those patients.