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t(9;12)(p24;p13) ETV6::JAK2

Written2014-03Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
This article is an update of :
1998-02Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
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 1122

Clinics and Pathology

Disease Myeloproliferative disease in transformation, myelodysplastic syndrome (MDS), B-cell acute leukemia (B-ALL), and T-cell acute leukemia (T-ALL).
Phenotype / cell stem origin One B-ALL was CD10+, the two others were not otherwise specified. The myeloproliferative disease was an atypical chronic myelogenous leukemia (a-CML).
Epidemiology Seven patients to date: 5 male and 2 female patients. Median age was 26 years (range 1.5-80), with two children cases (one B-ALL and one T-ALL), and four cases were found in young adults (aged 25, 26, 32, 33) (Lacronique et al., 1997; Peeters et al., 1997; Najfeld et al. 2007; Zhou et al., 2012).
Prognosis Three patients did not reach complete remission (two B-ALL and one T-ALL); one patient died 6 months after diagnosis (the a-CML case), and one patient achieved CR, relapsed; a second CR was obtained and the patient was alive 31 months after diagnosis (a B-ALL case).


Cytogenetics Morphological The t(9;12)(p24;p13) was the sole abnormality in three cases, accompanied with a t(3;12) ETV6/MECOM in one case, with numerical abnormalities in one case, and part of a complex karyotype in one case (the MDS case). Del(6q) was found in two cases.

Genes involved and Proteins

Gene NameJAK2 (janus kinase 2)
Location 9p24.1
Dna / Rna 24 exons.
Protein 1132 amino acids (aa); from N-term to C-term, JAK2 contains: an interaction region with cytokine/interferon/growth hormone receptors: aa 1-239, a FERM domain: aa 37-380, a SH2 domain: aa 401-482, two protein kinase domains: aa 545-809 and 849-1124, an ATP nucleotide binding site: aa 855-863, and a loop structure: aa 1056-1078 (JAK2 kinase insertion loop). JAK homology domains are the following: JH7: aa 25-137; JH6: aa 144-284; JH5: aa 288-309; JH4: aa 322-440; JH3: aa 451-538; JH2: aa 543-824; JH1: 836-1123. Phosphotyrosines are located at aa 119, 372, 373, 523, 813, 868, 966, 972, 1007, and 1008 (Harpur et al., 1992; Saltzman et al., 1998; Lucet et al., 2006). Protein tyrosine kinase of the non-receptor type that associates with the intracellular domains of cytokine receptors; Mediates signaling transduction.
Gene NameETV6 (ets variant 6)
Location 12p13.2
Dna / Rna 9 exons; alternate splicing.
Protein 452 amino acids. ETV6 is composed of a HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term (binds to the DNA sequence 5'-CCGGAAGT-3'). Transcriptional regulator; tumor suppressor. Involved in bone marrow hematopoiesis.

Result of the chromosomal anomaly

Hybrid gene
Description 5' ETV6 - 3' JAK2. Three different hybrids have been found: fusion of ETV6 exon 4 to JAK2 exon 17 (Peeters et al., 1997), fusion of ETV6 exon 5 to JAK2 exon 17 (Lacronique et al., 1997), and fusion of ETV6 exon 5 to JAK2 exon 12 (Peeters et al., 1997).
Fusion Protein
  ETV6/JAK2 fusion protein.
Description The HLH domain of ETV6 is fused to the protein kinase domain(s), the ATP nucleotide binding, and the loop structure of JAK2; according to the different possible breakpoints, the resulting protein contains 475, 654, or 876 amino acids. Furthermore, other products result from splicing (Peeters et al., 1997). The reciprocal JAK2-ETV6 may not be expressed.
Oncogenesis It may be speculated that the HLH domain of ETV6 induces oligomerization, resulting in constitutive activation of the kinase domain of JAK2.

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


JAK2, a third member of the JAK family of protein tyrosine kinases.
Harpur AG, Andres AC, Ziemiecki A, Aston RR, Wilks AF.
Oncogene. 1992 Jul;7(7):1347-53.
PMID 1620548
A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.
Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA.
Science. 1997 Nov 14;278(5341):1309-12.
PMID 9360930
The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.
Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF, Rossjohn J.
Blood. 2006 Jan 1;107(1):176-83. Epub 2005 Sep 20.
PMID 16174768
Numerical gain and structural rearrangements of JAK2, identified by FISH, characterize both JAK2617V>F-positive and -negative patients with Ph-negative MPD, myelodysplasia, and B-lymphoid neoplasms.
Najfeld V, Cozza A, Berkofsy-Fessler W, Prchal J, Scalise A.
Exp Hematol. 2007 Nov;35(11):1668-76.
PMID 17976519
Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.
Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P.
Blood. 1997 Oct 1;90(7):2535-40.
PMID 9326218
Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue.
Saltzman A, Stone M, Franks C, Searfoss G, Munro R, Jaye M, Ivashchenko Y.
Biochem Biophys Res Commun. 1998 May 29;246(3):627-33.
PMID 9618263
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


This paper should be referenced as such :
JL Huret
t(9;12)(p24;p13) ETV6/JAK2
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):757-759.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. t(9;12)(p24;p13). Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):54-54.

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

Genes ETV6 GAB2 JAK2

Translocations implicated (Data extracted from papers in the Atlas)

 t(9;12)(p24;p13) ETV6/JAK2

External links

ETV6 (12p13.2) JAK2 (9p24.1)

ETV6 (12p13.2) JAK2 (9p24.1)

Mitelman databaset(9;12)(p24;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 ( 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::JAK2 [MCList]  ETV6 (12p13.2) JAK2 (9p24.1)
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