Functional analysis of truncated forms of ETV6

Alister WardTitle: Functional analysis of truncated forms of ETV6

Authors: Rasighaemi, Parisa; Liongue, Clifford; Onnebo, Sara M. N.; Ward, Alister C.

Source: BRITISH JOURNAL OF HAEMATOLOGY, 171 (4):658-662, NOV 2015

First paragraph of the paper: The ETV6 (TEL) transcription factor has been shown to play a wide role in haematopoiesis, influencing the development of multiple lineages, while chromosomal translocations involving fusions of the ETV6 gene occur frequently in haematological malignancies (Rasighaemi et al, 2014). Recurrent mutations of ETV6 have been reported in cases of acute myeloid leukaemia (AML) (Barjesteh Van Waalwijk Van Doorn-Khosravaniet al, 2005; Silva et al, 2008), childhood B cell acute lymphoblastic leukaemia (B-ALL) (Zhang et al, 2011) and early immature adult T-cell ALL (T-ALL) (Van Vlierberghe et al, 2011), along with alternative splicing of ETV6 in myelodysplastic syndrome (MDS) (Sasaki et al, 2004). These lead to expression of alternate forms of ETV6 lacking either the N-terminal PNT domain, involved in protein–protein interactions, or the C-terminal ETS DNA-binding domain, unable to repress transcription but capable of ablating the repressional activity of full-length ETV6 in vitro (Barjesteh Van Waalwijk Van Doorn-Khosravani et al, 2005; Van Vlierberghe et al, 2011). However, the in vivo role of these ETV6 truncations has not been characterized. The zebrafish represents an established model for the study of haematopoiesis and its perturbation, which has previously been used to investigate the role of ETV6 (Rasighaemi et al, 2015), and the consequences of enforced expression of ETV6-JAK2 (Onnebo et al,2012).

This study has utilized this model to analyse the in vivo function of truncated ETV6 proteins.