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

被引:18
作者
Zambuzi Cardoso Marsola, Ana Paula [1 ]
Simoes, Belinda Pinto [2 ]
Palma, Leonardo Carvalho [2 ]
Berzoti-Coelho, Maria Gabriela [1 ]
Burin, Sandra Mara [1 ]
de Castro, Fabiola Attie [1 ]
机构
[1] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Sch Pharmaceut Sci Ribeirao Preto, Cafe Ave, Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, 3900 Bandeirantes Ave, Ribeirao Preto, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Chronic myeloid leukemia; BCR-ABL1; Tyrosine kinase inhibitors; Hippo pathway; Aurora kinases; CHRONIC MYELOGENOUS LEUKEMIA; DAMAGE-INDUCED APOPTOSIS; TUMOR-SUPPRESSOR LATS1; DNA-DAMAGE; HOMOLOG; YAP; PHOSPHORYLATION; ONCOGENE; ENCODES;
D O I
10.1007/s12032-018-1079-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 myelo-proliferation 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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页数:10
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