ETV6 (TEL1) in Blood Cell Development and Malignancy

Mini Review

J Blood Disord. 2014;1(3): 7.

ETV6 (TEL1) in Blood Cell Development and Malignancy

Parisa Rasighaemi1, Clifford Liongue1,2 and Alister C Ward1,2*

1School of Medicine, Deakin University, Australia

2Strategic Research Centre in Molecular and Medical Research, Deakin University, Australia

*Corresponding author: Alister C Ward, School of Medicine, Deakin University, Pigdons Road, Geelong, Victoria 3216, Australia.

Received: September 25, 2014; Accepted: October 27, 2014; Published: October 27, 2014


The ETV6 (TEL1) gene encodes a member of the ETS family of transcriptional regulators. It represents one of the most frequently disrupted genes in haematological malignancies, with over 50 different translocations described. Moreover, deletion, silencing or truncating mutations have also been reported, suggesting a potential tumor suppressor function. Recent studies have shown that ETV6 plays a broad and complex role in early hematopoiesis, impacting on the development of multiple lineages, providing new insights into how its perturbation contributes to disease.

Keywords: ETV6; TEL1; ETS; Hematopoiesis; Leukemia


AML: Acute Myelogenous Leukemia; AEL: Acute Eosinophilic Leukemia; ALL: Acute Lymphocytic Leukemia; Bc: Blastic crisis; BP: Blastic Phase; CIM: Chronic Idiopathic Myelofibrosis; CML: Chronic Myelogenous Leukemia; CMML: Chronic Myelomonocytic Leukemia; CP: Chronic Phase; ETS: E26-Transforming Specific; ETV: ETS Variant; HDAC: Histone Deacetylase; HLH: Helix-Loop-Helix; MDS: Myelodysplastic Syndrome; MPN: Myeloproliferative Neoplasm; Ph: Philadelphia chromosome; PNT: Pointed; PV: Polycythemia Vera; RA: Refractory Anemia; RAEB: Refractory Anemia with excess of Blasts; TCL: T Cell Leukemia; TEL: Translocating E26 transformingspecific Leukemia


ETV6 (ETS variant 6) also known as TEL1 (Translocating E26 transforming-specific leukemia 1) and the related ETV7 or TEL2 are members of the evolutionarily-conserved ETS (E26-transforming specific) family of transcription factors, which have been implicated in a variety of cellular development and differentiation processes [1,2]. All ETS proteins share an extensively conserved domain of about 85 amino acids, which binds to purine-rich sequences within the promoters or enhancers of target genes, utilizing a GGAA/T sequence that is flanked by 5-8 nucleotide, thus determining the specificity of each family member [3,4]. This so-called ETS domain represents a winged helix-turn-helix domain composed of 3 α-helixes and 4 β-sheets arranged in the order α1-β1-β2-α2-α3-β3-β4 [5]. Another evolutionary conserved domain shared by a subset of ETS family members is the Pointed (PNT) domain, which is in the form of a modified Helix-Loop-Helix (HLH) structure for mediating proteinprotein interactions [6]. Although some ETS family members are expressed ubiquitously, others are predominantly expressed in a tissue-specific manner [7], including in hematopoietic cells where they regulate blood cell development [8].

ETV6 gene and protein structure and function

The human ETV6 gene spans a region of over 240 kb on the short (P) arm of chromosome 12 at band 13.1 and consists of 8 exons [9]. There are two isoforms of ETV6 (57 kDa and 53 kDa) arising from alternative start codons in exon 1a (Figure 1) [10]. The PNT domain at its N-terminus is encoded by exons 3 and 4 and the ETS domain at its C-terminus is encoded by exons 6 and 7 flanking a central domain encoded by exon 5 (Figure 1).