Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo

Author:

Mayumi Azusa1ORCID,Imamura Toshihiko1,Yoshida Hideki1,Osone Shinya1,Yasuda Takahiko2,Iehara Tomoko1

Affiliation:

1. Department of Paediatrics Kyoto Prefectural University of Medicine Kyoto Japan

2. Clinical Research Center Nagoya Medical Centre National Hospital Organization Nagoya Japan

Abstract

AbstractETV6::Fyn‐related kinase (FRK), which is a Src family tyrosine‐kinase‐related fusion gene and firstly identified in our patient with paediatric high risk B cell precursor acute lymphoblastic leukaemia (B‐ALL), has no evidence of efficacy of tyrosine kinase inhibitor in vivo. We performed functional analysis of ETV6::FRK to establish molecular targeting therapy and determined that dasatinib could abrogate proliferation activity of ETV6::FRK through the repression of FRK‐STAT3/STAT5 pathway in vitro and significantly extended the survival time of the xenografted mice in vivo (p < 0.01). Our data support the potential of dasatinib as a therapeutic option for patients with B‐ALL harboring FRK rearrangements.

Publisher

Wiley

Subject

General Earth and Planetary Sciences

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