t(9;12)(q34;p13) ETV6/ABL1

2014-03-01   Etienne De Braekeleer , Etienne De Braekeleer , Etienne De Braekeleer 

1.Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France
2.The Ohio State University, Division of Clinical Pathology, Department of Pathology, 167 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210, USA

Clinics and Pathology


Malignant hemopathies (26 cases reported)

Phenotype stem cell origin

AML (3 cases), B-cell ALL (8 cases), T-cell ALL (1 case), RAEB evolving into AML (1 case), chronic myeloproliferative neoplasm (2 cases), Philadelphia chromosome-negative CML (11 cases).


Gender: 17 males, 8 females; age at diagnosis: 8 months to 81 years.


Eosinophilia appears to be a common feature of malignancies associated with the ETV6-ABL1 fusion gene (15/20 cases).


The t(9;12)(q34;p13) involves the ETV6 gene (12p13), a transcription factor frequently rearranged in myeloid and lymphoid leukemias. More than 30 ETV6 fusion gene partners have been described. Most translocations involving ETV6 generate fusion genes that lead to the activation of transcription factors or kinases but other mechanisms are also known (loss of function of the fusion gene affecting ETV6 and the partner gene, activation of a proto-oncogene in the vicinity of a chromosomal translocation and dominant negative effect of the fusion protein over transcriptional repression mediated by wild-type ETV6).


Cytogenetics morphological

t(9;12)(q34;p13) is very difficult to be identified by conventional cytogenetics.

Cytogenetics molecular

t(9;12)(q34;p13) usually requires FISH analysis with ETV6 and ABL1 probes to be detected (cryptic translocation). Insertions are also frequently identified.

Additional anomalies

Additional anomalies are frequent but show no consistent features (trisomies and monosomies of various chromosomes, structural rearrangements including deletions and translocations).


t(9;12;14)(q34;p13;q22) (seen in conventional cytogenetics),
t(8;9;12)(p12;q34;p13) (seen in conventional cytogenetics),
ins(9;12)(q34;p13p13) (seen by molecular cytogenetics),
ins(12;9)(p13;q34q34) (seen by molecular cytogenetics).

Genes Involved and Proteins

Gene name
ETV6 (ets variant 6)
The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias.
Dna rna description
The ETV6 gene spans a region of less than 250 kb at band 12p13.1 and consists of 8 exons. There are two start codons, one (exon 1a starting at codon 1) located at the beginning of the gene and another alternative (exon 1b starting at codon 43) upstream of exon 3.
Protein description
The ETV6 protein (452 amino acids) contains two major domains, the HLH (helix-loop-helix) and ETS domains. The HLH domain, also referred to as the pointed or sterile alpha motif domain, is encoded by exons 3 and 4 and functions as a homo-oligodimerization domain. The ETS domain, encoded by exons 6 through 8, is responsible for sequence specific DNA-binding and protein-protein interaction.
Gene name
ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Dna rna description
The ABL1 gene, spanning a 230-kb region at band 9q34, includes the 5 alternative first exons 1b and 1a and ten common exons numbered from 2 to 11. Alternative splicing using exons 1b and 1a gives rise to mRNA of 7 and 6 kb, respectively.
Protein description
The ABL1 protein has three SRC homology (SH) domains called SH1, SH2 and SH3, of which SH1 that has a tyrosine kinase function. The SH2 and SH3 domains are involved in protein-protein interactions, which regulate the tyrosine kinase activity; they are necessary for signal transduction function. The ABL1 protein has also three nuclear localization signal domains and three DNA binding regions and an F-actin binding domain.

Result of the Chromosomal Anomaly


Two ETV6-ABL1 transcripts were identified in most of the patients, one joining exon 5 of ETV6 to exon 2 of ABL1, the other, usually found at very low levels, joining ETV6 exon 4 to ABL1 exon 2.
Atlas Image
Schematic diagram of the ETV6, ABL1 and ETV6-ABL1 proteins.


The fusion protein retains all three SH domains, including the tyrosine kinase domain, of ABL1, which make these patients sensitive to tyrosine kinase inhibitors. The retained N-terminal part of the ETV6 protein contains the helix-loop-helix domain necessary for oligomerization of the protein, which is required for tyrosine kinase activation, cytoskeletal localization and neoplastic transformation.


Constitutive tyrosine kinase activation of ABL1.


Pubmed IDLast YearTitleAuthors
93658381997BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion.Andreasson P et al
87439901996Genomic organization of TEL: the human ETS-variant gene 6.Baens M et al
186566922008Establishment and cytogenetic characterization of a human acute lymphoblastic leukemia cell line (ALL-VG) with ETV6/ABL1 rearrangement.Baeumler J et al
128233492003Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate.Barbouti A et al
225787742012ETV6 fusion genes in hematological malignancies: a review.De Braekeleer E et al
87548091996Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia.Golub TR et al
186156812008Chronic phase of ETV6-ABL1 positive CML responds to imatinib.Kawamata N et al
194809352009Insertion (12;9)(p13;q34q34): a cryptic rearrangement involving ABL1/ETV6 fusion in a patient with Philadelphia-negative chronic myeloid leukemia.Kelly JC et al
125052592002Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature.Keung YK et al
121613532002Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia.La Starza R et al
118402982002Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient.Lin H et al
206183342010A doctor(s) dilemma: ETV6-ABL1 positive acute lymphoblastic leukaemia.Malone A et al
111753682000Proteins of the ETS family with transcriptional repressor activity.Mavrothalassitis G et al
157890672005Broad molecular screening of an unclassifiable myeloproliferative disorder reveals an unexpected ETV6/ABL1 fusion transcript.Meyer-Monard S et al
173665482007A fifteen-year cytogenetic remission following interferon treatment in a patient with an indolent ETV6-ABL positive myeloproliferative syndrome.Mozziconacci MJ et al
193946932009Myeloproliferative disorder with eosinophilia and ETV6-ABL gene rearrangement: efficacy of second-generation tyrosine kinase inhibitors.Nand R et al
119643202002Transient response to imatinib mesylate (STI571) in a patient with the ETV6-ABL t(9;12) translocation.O'Brien SG et al
78050371995The novel activation of ABL by fusion to an ets-related gene, TEL.Papadopoulos P et al
211934232011ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibition.Perna F et al
156761522005Molecular and cytogenetic characterization of a novel rearrangement involving chromosomes 9, 12, and 17 resulting in ETV6 (TEL) and ABL fusion.Tirado CA et al
111702852001Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia.Van Limbergen H et al
223735492012Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.Zhou MH et al
205899322010Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: poor prognosis and prenatal origin.Zuna J et al


Fusion gene

ETV6/ABL1 ETV6 (12p13.2) ABL1 (9q34.12) M ins(12;9)(p13;q34q34) ins(9;12)(q34;p13p13) t(9;12)(q34;p13) t(9;12;14)(q34;p13;q22)|ETV6/ABL1 ETV6 (12p13.2) ABL1 (9q34.12) TIC


Etienne De Braekeleer ; Etienne De Braekeleer ; Etienne De Braekeleer

t(9;12)(q34;p13) ETV6/ABL1

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1080/t(9;12)(q34;p13)-etv6-abl1

Historical Card

2000-12-01 t(9;12)(q34;p13) ETV6/ABL1 by  Nyla A Heerema 

The Ohio State University, Division of Clinical Pathology, Department of Pathology, 167 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210, USA

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