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

2014-03-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


Myeloproliferative disease in transformation, myelodysplastic syndrome (MDS), B-cell acute leukemia (B-ALL), and T-cell acute leukemia (T-ALL).

Phenotype stem cell origin

One B-ALL was CD10+, the two others were not otherwise specified. The myeloproliferative disease was an atypical chronic myelogenous leukemia (a-CML).


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).


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).

Genes Involved and Proteins

Gene name
JAK2 (janus kinase 2)
Dna rna description
24 exons.
Protein description
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 name
ETV6 (ets variant 6)
Dna rna description
9 exons; alternate splicing.
Protein description
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


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).
Atlas Image
ETV6/JAK2 fusion protein.


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.


It may be speculated that the HLH domain of ETV6 induces oligomerization, resulting in constitutive activation of the kinase domain of JAK2.


Pubmed IDLast YearTitleAuthors
16205481992JAK2, a third member of the JAK family of protein tyrosine kinases.Harpur AG et al
93609301997A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.Lacronique V et al
161747682006The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.Lucet IS et al
179765192007Numerical 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 et al
93262181997Fusion 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 et al
96182631998Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue.Saltzman A et al
223735492012Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.Zhou MH et al


Fusion gene

ETV6/JAK2 ETV6 (12p13.2) JAK2 (9p24.1) M t(9;12)(p24;p13) t(9;15;12)(p24;q15;p13)|ETV6/JAK2 ETV6 (12p13.2) JAK2 (9p24.1) TIC


Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1122/t(9;12)(p24;p13)

Historical Card

1998-02-01 t(9;12)(p24;p13) ETV6/JAK2 by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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