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Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells.
Parducci, Natália Sudan; Garnique, Anali Del Milagro Bernabe; Lima, Keli; Carlos, Jorge Antonio Elias Godoy; Fonseca, Natasha Peixoto; de Miranda, Lívia Bassani Lins; de Almeida, Bruna Oliveira; Rego, Eduardo Magalhães; Traina, Fabiola; Machado-Neto, João Agostinho.
Afiliação
  • Parducci NS; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Garnique ADMB; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Lima K; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, Universi
  • Carlos JAEG; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Fonseca NP; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil.
  • de Miranda LBL; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • de Almeida BO; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Rego EM; Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil; Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão
  • Traina F; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Cell Based Therapy, São Paulo Research Foundation, Ribeirão Preto, SP, Brazil.
  • Machado-Neto JA; Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil. Electronic address: jamachadoneto@usp.br.
Blood Cells Mol Dis ; 104: 102799, 2024 01.
Article em En | MEDLINE | ID: mdl-37839173
ABSTRACT
Myeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCRABL1 and JAK2V617F increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCRABL1 and JAK2V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3RT618I-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3RT618I mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced histone H3 phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced PARP1 cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aurora Quinase A / Antineoplásicos Limite: Humans Idioma: En Revista: Blood Cells Mol Dis Assunto da revista: HEMATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aurora Quinase A / Antineoplásicos Limite: Humans Idioma: En Revista: Blood Cells Mol Dis Assunto da revista: HEMATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos