Open AccessPretreatment evaluation of fluorescence resonance energy transfer‐based drug sensitivity test for patients with chronic myelogenous leukemia treated with dasatinib
Author(s) -
Kondo Takeshi,
Fujioka Mari,
Tsuda Masumi,
Murai Kazunori,
Yamaguchi Kohei,
Miyagishima Takuto,
Shindo Motohiro,
Nagashima Takahiro,
Wakasa Kentaro,
Fujimoto Nozomu,
Yamamoto Satoshi,
Yonezumi Masakatsu,
Saito Souichi,
Sato Shinji,
Ogawa Kazuei,
Chou Takaaki,
Watanabe Reiko,
Kato Yuichi,
Takahashi Shuichiro,
Okano Yoshiaki,
Yamamoto Joji,
Ohta Masatsugu,
Iijima Hiroaki,
Oba Koji,
Kishino Satoshi,
Sakamoto Junichi,
Ishida Yoji,
Ohba Yusuke,
Teshima Takanori
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13625
Subject(s) - dasatinib , förster resonance energy transfer , medicine , abl , chronic myelogenous leukemia , tyrosine kinase inhibitor , tyrosine kinase , cancer research , oncology , pharmacology , leukemia , fluorescence , cancer , receptor , physics , quantum mechanics
Tyrosine kinase inhibitors ( TKI ) are used for primary therapy in patients with newly diagnosed CML . However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a FRET ‐based drug sensitivity test in which a CrkL‐derived fluorescent biosensor efficiently quantifies the kinase activity of BCR ‐ ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR ‐ ABL . Here, we validated the utility of the FRET ‐based drug sensitivity test carried out at diagnosis for predicting the molecular efficacy. Sixty‐two patients with newly diagnosed chronic phase CML were enrolled in this study and treated with dasatinib. Bone marrow cells at diagnosis were subjected to FRET analysis. The Δ FRET value was calculated by subtraction of FRET efficiency in the presence of dasatinib from that in the absence of dasatinib. Treatment response was evaluated every 3 months by the BCR ‐ ABL 1 International Scale. Based on the Δ FRET value and molecular response, a threshold of the Δ FRET value in the top 10% of FRET efficiency was set to 0.31. Patients with Δ FRET value ≥0.31 had significantly superior molecular responses ( MMR at 6 and 9 months and both MR 4 and MR 4.5 at 6, 9, and 12 months) compared with the responses in patients with Δ FRET value <0.31. These results suggest that the FRET ‐based drug sensitivity test at diagnosis can predict early and deep molecular responses. This study is registered with UMIN Clinical Trials Registry ( UMIN 6358).