論文

査読有り
2019年5月

TOPK is regulated by PP2A and BCR/ABL in leukemia and enhances cell proliferation.

Int. J. Oncol.
  • Emi Uchida
  • ,
  • Shihoko Suwa
  • ,
  • Ryoto Yoshimoto
  • ,
  • Ken Watanabe
  • ,
  • Takeshi Kasama
  • ,
  • Osamu Miura
  • ,
  • Tetsuya Fukuda

記述言語
英語
掲載種別
DOI
10.3892/ijo.2019.4740

Although treatment of chronic myeloid leukemia (CML) has improved with the development of tyrosine kinase inhibitors (TKIs), patients develop fatal blast crisis (BC) whilst receiving TKI treatment. Alternative treatments for cases resistant to TKIs are required. A serine/threonine protein kinase, T‑lymphokine‑activated killer cell‑originated protein kinase (TOPK), is highly expressed in various malignant tumors. Binding of peptides to human leukocyte antigen was assessed via mass spectrometry in K562 CML cells. TOPK expression was assessed in various CML cell lines and in clinical samples obtained from patients with CML using reverse transcription‑quantitative polymerase chain reaction and western blot assays. It was observed that TOPK was expressed abundantly in BCR/ABL‑positive cell lines and at significantly higher levels in CML clinical samples compared with healthy donor samples. Overexpression of BCR/ABL or the presence of its inhibitor imatinib upregulated and downregulated TOPK expression, respectively, indicating that TOPK may be a target of BCR/ABL. TOPK inhibitor OTS514 suppressed proliferation of BCR/ABL‑positive cell lines and colony formation of CD34‑p

リンク情報
DOI
https://doi.org/10.3892/ijo.2019.4740
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30864683