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

Written2014-03Etienne De Braekeleer, Nathalie Douet-Guilbert, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France
This article is an update of :
2000-12Nyla 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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ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1080

Clinics and Pathology

Disease Malignant hemopathies (26 cases reported)
Phenotype / cell stem 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).
Epidemiology Gender: 17 males, 8 females; age at diagnosis: 8 months to 81 years.
Clinics 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).


Note t(9;12)(q34;p13) as the sole abnormality or associated with other abnormalities.
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).
Variants 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

Note As both genes have opposite orientation in relation to the centromeres, an in frame ETV6-ABL1 fusion gene requires at least three chromosomal breaks to be generated.
Gene NameETV6 (ets variant 6)
Location 12p13.2
Note The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias.
Dna / Rna 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 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 NameABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Location 9q34.12
Dna / Rna 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 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

Hybrid gene
Transcript 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.
Fusion Protein
  Schematic diagram of the ETV6, ABL1 and ETV6-ABL1 proteins.
Description 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.
Oncogenesis Constitutive tyrosine kinase activation of ABL1.


BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion.
Andreasson P, Johansson B, Carlsson M, Jarlsfelt I, Fioretos T, Mitelman F, Hoglund M.
Genes Chromosomes Cancer. 1997 Nov;20(3):299-304.
PMID 9365838
Genomic organization of TEL: the human ETS-variant gene 6.
Baens M, Peeters P, Guo C, Aerssens J, Marynen P.
Genome Res. 1996 May;6(5):404-13.
PMID 8743990
Establishment and cytogenetic characterization of a human acute lymphoblastic leukemia cell line (ALL-VG) with ETV6/ABL1 rearrangement.
Baeumler J, Szuhai K, Falkenburg JH, van Schie ML, Ottmann OG, Nijmeijer BA.
Cancer Genet Cytogenet. 2008 Aug;185(1):37-42. doi: 10.1016/j.cancergencyto.2008.05.001.
PMID 18656692
Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate.
Barbouti A, Ahlgren T, Johansson B, Hoglund M, Lassen C, Turesson I, Mitelman F, Fioretos T.
Br J Haematol. 2003 Jul;122(1):85-93.
PMID 12823349
A TEL/ABL fusion gene on chromosome 12p13 in a case of Ph-, BCR-atypical CML.
Brunel V, Sainty D, Carbuccia N, Mozzicconacci M, Fernandez F, Simonetti J, Gabert J, Dubreuil P, Lafage-Pochitaloff M, Birg F.
Leukemia 1996; 10: 2003.
ETV6 fusion genes in hematological malignancies: a review.
De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Basinko A, De Braekeleer M.
Leuk Res. 2012 Aug;36(8):945-61. doi: 10.1016/j.leukres.2012.04.010. Epub 2012 May 12. (REVIEW)
PMID 22578774
Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia.
Golub TR, Goga A, Barker GF, Afar DE, McLaughlin J, Bohlander SK, Rowley JD, Witte ON, Gilliland DG.
Mol Cell Biol. 1996 Aug;16(8):4107-16.
PMID 8754809
Chronic phase of ETV6-ABL1 positive CML responds to imatinib.
Kawamata N, Dashti A, Lu D, Miller B, Koeffler HP, Schreck R, Moore S, Ogawa S.
Genes Chromosomes Cancer. 2008 Oct;47(10):919-21. doi: 10.1002/gcc.20593.
PMID 18615681
Insertion (12;9)(p13;q34q34): a cryptic rearrangement involving ABL1/ETV6 fusion in a patient with Philadelphia-negative chronic myeloid leukemia.
Kelly JC, Shahbazi N, Scheerle J, Jahn J, Suchen S, Christacos NC, Mowrey PN, Witt MH, Hostetter A, Meloni-Ehrig AM.
Cancer Genet Cytogenet. 2009 Jul;192(1):36-9. doi: 10.1016/j.cancergencyto.2009.02.012.
PMID 19480935
Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature.
Keung YK, Beaty M, Steward W, Jackle B, Pettnati M.
Cancer Genet Cytogenet. 2002 Oct 15;138(2):139-42. (REVIEW)
PMID 12505259
Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia.
La Starza R, Trubia M, Testoni N, Ottaviani E, Belloni E, Crescenzi B, Martelli M, Flandrin G, Pelicci PG, Mecucci C.
Haematologica. 2002 Aug;87(8):789-94.
PMID 12161353
Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient.
Lin H, Guo JQ, Andreeff M, Arlinghaus RB.
Leukemia. 2002 Feb;16(2):294-7.
PMID 11840298
A doctor(s) dilemma: ETV6-ABL1 positive acute lymphoblastic leukaemia.
Malone A, Langabeer S, O'Marcaigh A, Storey L, Bacon CL, Smith OP.
Br J Haematol. 2010 Oct;151(1):101-2. doi: 10.1111/j.1365-2141.2010.08323.x. Epub 2010 Jul 7.
PMID 20618334
Proteins of the ETS family with transcriptional repressor activity.
Mavrothalassitis G, Ghysdael J.
Oncogene. 2000 Dec 18;19(55):6524-32. (REVIEW)
PMID 11175368
Broad molecular screening of an unclassifiable myeloproliferative disorder reveals an unexpected ETV6/ABL1 fusion transcript.
Meyer-Monard S, Muhlematter D, Streit A, Chase AJ, Gratwohl A, Cross NC, Jotterand M, Tichelli A.
Leukemia. 2005 Jun;19(6):1096-9.
PMID 15789067
A fifteen-year cytogenetic remission following interferon treatment in a patient with an indolent ETV6-ABL positive myeloproliferative syndrome.
Mozziconacci MJ, Sainty D, Chabannon C.
Am J Hematol. 2007 Jul;82(7):688-9.
PMID 17366548
Myeloproliferative disorder with eosinophilia and ETV6-ABL gene rearrangement: efficacy of second-generation tyrosine kinase inhibitors.
Nand R, Bryke C, Kroft SH, Divgi A, Bredeson C, Atallah E.
Leuk Res. 2009 Aug;33(8):1144-6. doi: 10.1016/j.leukres.2009.03.011. Epub 2009 Apr 25.
PMID 19394693
Transient response to imatinib mesylate (STI571) in a patient with the ETV6-ABL t(9;12) translocation.
O'Brien SG, Vieira SA, Connors S, Bown N, Chang J, Capdeville R, Melo JV.
Blood. 2002 May 1;99(9):3465-7.
PMID 11964320
The novel activation of ABL by fusion to an ets-related gene, TEL.
Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM.
Cancer Res. 1995 Jan 1;55(1):34-8.
PMID 7805037
ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibition.
Perna F, Abdel-Wahab O, Levine RL, Jhanwar SC, Imada K, Nimer SD.
Haematologica. 2011 Feb;96(2):342-3. doi: 10.3324/haematol.2010.036673. Epub 2010 Dec 29.
PMID 21193423
Molecular and cytogenetic characterization of a novel rearrangement involving chromosomes 9, 12, and 17 resulting in ETV6 (TEL) and ABL fusion.
Tirado CA, Sebastian S, Moore JO, Gong JZ, Goodman BK.
Cancer Genet Cytogenet. 2005 Feb;157(1):74-7.
PMID 15676152
Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia.
Van Limbergen H, Beverloo HB, van Drunen E, Janssens A, Hahlen K, Poppe B, Van Roy N, Marynen P, De Paepe A, Slater R, Speleman F.
Genes Chromosomes Cancer. 2001 Mar;30(3):274-82.
PMID 11170285
Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.
Zhou MH, Gao L, Jing Y, Xu YY, Ding Y, Wang N, Wang W, Li MY, Han XP, Sun JZ, Wang LL, Yu L.
Ann Hematol. 2012 Aug;91(8):1235-43. doi: 10.1007/s00277-012-1431-4. Epub 2012 Feb 29.
PMID 22373549
Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: poor prognosis and prenatal origin.
Zuna J, Zaliova M, Muzikova K, Meyer C, Lizcova L, Zemanova Z, Brezinova J, Votava F, Marschalek R, Stary J, Trka J.
Genes Chromosomes Cancer. 2010 Oct;49(10):873-84. doi: 10.1002/gcc.20796.
PMID 20589932


This paper should be referenced as such :
Braekeleer E De, N Douet-Guilbert, Braekeleer M De
t(9;12)(q34;p13) ETV6/ABL1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(11):859-861.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Heerema, NA. t(9;12)(q34;p13). Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):42-43.

Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]

Genes ABL1 ETV6 GAB2

Translocations implicated (Data extracted from papers in the Atlas)

 t(9;12)(q34;p13) ETV6/ABL1

External links

ETV6 (12p13.2) ABL1 (9q34.12)

ETV6 (12p13.2) ABL1 (9q34.12)

Mitelman databaset(9;12)(q34;p13)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseETV6/ABL1 [MCList]  ETV6 (12p13.2) ABL1 (9q34.12)
TICdbETV6/ABL1  ETV6 (12p13.2) ABL1 (9q34.12)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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