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

Autor: Fabíola Attié de Castro, Sandra Mara Burin, LC Palma, Maria Gabriela Berzoti-Coelho, Ana Paula Zambuzi Cardoso Marsola, Belinda Pinto Simões
Rok vydání: 2018
Předmět:
Adult
Male
0301 basic medicine
Cancer Research
Protein Serine-Threonine Kinases
Biology
Philadelphia chromosome
Young Adult
03 medical and health sciences
0302 clinical medicine
Aurora kinase
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
hemic and lymphatic diseases
Biomarkers
Tumor
medicine
Aurora Kinase B
Humans
Hippo Signaling Pathway
Protein Kinase Inhibitors
neoplasms
Myeloproliferative neoplasm
Aged
Aurora Kinase A
Aged
80 and over
Hippo signaling pathway
Gene Expression Regulation
Leukemic
Myeloid leukemia
Hematology
General Medicine
Middle Aged
Cell cycle
Prognosis
medicine.disease
030104 developmental biology
Imatinib mesylate
Oncology
Drug Resistance
Neoplasm
Case-Control Studies
030220 oncology & carcinogenesis
Imatinib Mesylate
Cancer research
Female
Tyrosine kinase
Follow-Up Studies
Signal Transduction
Zdroj: Medical Oncology. 35
ISSN: 1559-131X
1357-0560
Popis: 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.
Databáze: OpenAIRE
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