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==Synonyms==
==Synonyms==
ETS Variant 6; TEL; THC5; TEL/ABL
"E26 transformation-specific variant 6"; "E-twenty-six variant 6"; ETS Variant 6; "Translocation-ETS-Leukemia"; TEL; THC5; TEL/ABL
==Genomic Location==
==Genomic Location==
==Cancer Category/Type==
==Cancer Category/Type==
chronic myelomonocytic leukemia t(5;12)(q33;p13) translocation ETV6-PDGFRB (Golub et al. (1994) translocation consisting of the 154 N terminal residues of ETV6 linked to the transmembrane and tyrosine kinase domains of the PDGFRB on chromosome 5q33.
''[http://www.ccga.io/index.php/Chronic_Myelomonocytic_Leukemia_(CMML) 'chronic myelomonocytic leukemia]'''
t(5;12)(q33;p13) translocation ETV6-PDGFRB (Golub et al. (1994) translocation consisting of the 154 N terminal residues of ETV6 linked to the transmembrane and tyrosine kinase domains of the PDGFRB on chromosome 5q33.
chronic myeloproliferative disorder ETV6/PDGFRB Apperley et al. (2002)
chronic myeloproliferative disorder ETV6/PDGFRB Apperley et al. (2002)
acute lymphocytic leukemia ETV6/RUNX1 Golub et al. (1995)
acute lymphocytic leukemia ETV6/RUNX1 Golub et al. (1995)
'''B-cell acute lymphoblastic leukemia (B-ALL)'''
t(12;21)(p13;q22); 25% of childhood B-cell acute lymphoblastic leukemia (B-ALL) bear an ETV6-RUNX1 translocation, but are much less common (on;y 2%) in adult B-cell acute lymphoblastic leukemia (B-ALL) [2]. The ETV6-RUNX1 trans -
location produces a fusion protein that confers a dominant negative effect on the normal RUNX1 protein function (Transcriptional activation become transcriptional repression) (1, 2]. The ETV6-RUNXT1 translocation confers a favourable prognosis with cures
seen in >90% of childhood B-ALL [1].
chronic eosinophilic leukaemia (CEL)
ETV6-PDGFRA fusion gene, both with the haematological features of CEL, responded to low-dose imatinib [1]
t(5;12)(q31~33;p12) with formation of an ETV6-PDGFRB fusion gene
In cases with t(5;12), and in the variant translocations, there is synthesis of an aberrant, constitutively activated tyrosine kinase. The haematological features are most often those of CMML (usually with eosinophilia) but some patients have been characterized as atypical chronic myeloid leukaemias (aCML) (usually with eosinophilia), CEL and MPN with eosinophilia
==Gene Overview==
==Gene Overview==
The ETV6 gene encodes one of 29 proteins in the ETS family of transcription factors ( "ETS" is from "E26 transformation-specific" or "E-twenty-six"). The Protein Etvs6 contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. The protein is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. ([https://www.ncbi.nlm.nih.gov/gene/2120 addapted form NCBI Gene description]).
The ETV6 gene encodes one of 29 proteins in the ETS family of transcription factors ( "ETS" is from "E26 transformation-specific" or "E-twenty-six"). The Etvs6 protein contains two functional domains: a N-terminal pointed (PNT) that is involved in protein-protein interactions with itself and other proteins, and a C-terminal, helix-loop-helix, DNA-binding domain (the ETS domain). Normally, the Etv6 protein acts as a transcriptional repressor and tumor supressor [2]. Familial genetic studies have shown that the protein is required for hematopoiesis and hematologic and other malignancies [3, 4]. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. ([https://www.ncbi.nlm.nih.gov/gene/2120 addapted from NCBI Gene description]). In most translocations, the N-terminal PNT domain of ETV6 is fused to a partner gene and acts as an aggregator for other proteins for a variety of effects, including transcriptional repression (eg, EVT6-RUNX1) [1, 2], constitutive Activated tyrosine kinases (eg, ETV6-PDGFRB) [1],
Transcriptional repressor; binds to the DNA sequence 5-CCGGAAGT-3. Plays a role in hematopoiesis and malignant transformation.
Transcriptional repressor; binds to the DNA sequence 5-CCGGAAGT-3. Plays a role in hematopoiesis and malignant transformation.
ETV6/BTL fusion
ETV6/BTL fusion
ETV6/JAK2 fusion
ETV6/JAK2 fusion
ETV6/RUNX1 fusion
ETV6/RUNX1 fusion t(12;21)(p13;q22); ETV6-RUNX1
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2. Schafer, E.S. . et al. (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
2. Schafer, E.S. . et al. (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
3. Hock, H. (2017). ETV6 in Hematopoiesis and Leukemia Predisposition. Semin Hematol. 54: 98-104. PMID 28637624 DOI: 10.1053/j.seminhematol.2017.04.005
3. Hock, H. et al. (2017). ETV6 in Hematopoiesis and Leukemia Predisposition. Semin Hematol. 54: 98-104. PMID 28637624 DOI: 10.1053/j.seminhematol.2017.04.005
4. Zhang, M.Y et al. (2015). Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy, Nature Genet. 47: 180–185. PMID 25581430 DOI: 10.1038/ng.3177
== Notes ==
== Notes ==