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

Abstract

Abstract ETV6::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.

Keywords

• acute lymphoblastic leukaemia
• B‐ALL
• dasatinib
• ETV6::FRK