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Expression of Hippo signaling pathway and Aurora kinase genes in chronic myeloid leukemia

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Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from clonal expansion of hematopoietic stem cells positive for the Philadelphia chromosome. The CML pathogenesis is associated with expression of the BCR–ABL1 oncogene, which encodes the Bcr–Abl protein with tyrosine kinase activity, promoting the leukemic cell exacerbated myeloproliferation and resistance to apoptosis. CML patients are usually treated with tyrosine kinase inhibitors (TKI), but some of them acquire resistance or are refractory to TKI. Thus, it is still relevant to elucidate the CML pathogenesis and seek new therapeutic targets, such as the Hippo signaling pathway and cell cycle regulatory genes from the Aurora kinase family. The present study quantified the expression level of genes encoding components of the Hippo signaling pathway (LATS1, LATS2, YAP, and TAZ), AURKA and AURKB in CML patients at different stages of the disease, who were resistant or sensitive to imatinib mesylate therapy, and in healthy individuals. The expression levels of the target genes were correlated with the CML Sokal’s prognostic score. The most striking results were the LATS2 and AURKA overexpression in CML patients, the overexpression of TAZ and AURKB in CML patients at advanced phases and TAZ in CML IM-resistant. The development of drugs and/or identification of tumor markers for the Hippo signaling pathway and the Aurora kinase family, either alone or in combination, can optimize CML treatment by enhancing the susceptibility of leukemic cells to apoptosis and leading to a better disease prognosis.

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Funding

This work was supported by Coordination for the Improvement of Higher Education Personnel (CAPES) and FAPESP (2015-23555-3 and 2015-21237-4).

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Authors and Affiliations

  1. Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo-USP, Café Avenue, Ribeirão Preto, SP, Brazil

    Ana Paula Zambuzi Cardoso Marsola, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin & Fabíola Attié de Castro

  2. Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo-USP, 3900 Bandeirantes Avenue, Ribeirão Preto, SP, Brazil

    Belinda Pinto Simões & Leonardo Carvalho Palma

Authors
  1. Ana Paula Zambuzi Cardoso Marsola
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  2. Belinda Pinto Simões
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  3. Leonardo Carvalho Palma
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  4. Maria Gabriela Berzoti-Coelho
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  5. Sandra Mara Burin
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  6. Fabíola Attié de Castro
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Correspondence to Ana Paula Zambuzi Cardoso Marsola.

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All procedures performed in studies involving human participants complied with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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All the patients and healthy individuals who participated in this study signed the Informed Consent Form.

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Marsola, A.P.Z.C., Simões, B.P., Palma, L.C. et al. Expression of Hippo signaling pathway and Aurora kinase genes in chronic myeloid leukemia. Med Oncol 35, 26 (2018). https://doi.org/10.1007/s12032-018-1079-6

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  • DOI: https://doi.org/10.1007/s12032-018-1079-6

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