論文

査読有り
2017年2月2日

Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells.

Cell structure and function
  • Mika Horiguchi
  • Mari Fujioka
  • Takeshi Kondo
  • Yoichiro Fujioka
  • Xinxin Li
  • Kosui Horiuchi
  • Aya O Satoh
  • Prabha Nepal
  • Shinya Nishide
  • Asuka Nanbo
  • Takanori Teshima
  • Yusuke Ohba
  • 全て表示

42
1
開始ページ
15
終了ページ
26
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1247/csf.16019
出版者・発行元
JAPAN SOC CELL BIOLOGY

Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells. The biosensor harbors CrkL, one of the major substrates of BCR-ABL, and is therefore named Pickles after phosphorylation indicator of CrkL en substrate. The efficacy of this technique as a clinical test has been demonstrated, but the number of cells available for analysis is limited in a case-dependent manner, owing to the cleavage of the biosensor in patient-derived leukemia cells. Here, we describe an improved biosensor with an amino acid substitution and a nuclear export signal being introduced. Of the two predicted cleavage positions in CrkL, the mutations inhibited one cleavage completely and the other cleavage partially, thus collectively increasing the number of cells available for drug evaluation. This improved version of the biosensor holds promise in the future development of companion diagnostics to predict responses to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

リンク情報
DOI
https://doi.org/10.1247/csf.16019
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27928132
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000396394500002&DestApp=WOS_CPL
ID情報
  • DOI : 10.1247/csf.16019
  • ISSN : 0386-7196
  • eISSN : 1347-3700
  • PubMed ID : 27928132
  • Web of Science ID : WOS:000396394500002

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