t(5;12)(q31;p13) ETV6/ACSL6 in MDS,AML and AEL

2007-03-01   Maria D. Odero 

1.Departamento de Genetica, Facultades de Ciencias y Medicina, y Area de Oncologia, Centro de Investigacion Medica Aplicada (CIMA), Universidad de Navarra, 31008-Pamplona, Espana

Clinics and Pathology


The t(5;12)(q31;p13) translocation involving ETV6 (12p13) and ACSL6 (5q31) was found in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL).

Phenotype stem cell origin

Myeloid lineage


To date, one case with myelodysplastic syndrome (RAEB), one case with AML, one case with AEL, one case with atypical CML, and 2 cases with Polycythemia Vera (PV).
The t(5;12)(q31;p13) is a recurrent translocation in myeloid malignancies (at least 23 cases reported).


No prognostic value established.


Cytogenetics morphological

May be not easy to detect.

Cytogenetics molecular

The translocation can be detected by FISH with ETV6 probes. The ETV6 gene is rearranged, and the breakpoint is between exon 1 and exon 2 in all cases reported.

Additional anomalies

Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis.


No variants

Genes Involved and Proteins

Gene name
ETV6 (ets variant 6)
The gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma .
Dna rna description
9 exons; alternate splicing
Protein description
The gene encodes an ETS family transcription factor; the product of this gene contains a N-terminal pointed (PNT) domain that is involved in the protein-protein interactions, and a C-terminal ETS DNA-binding domain; wide expression; nuclear localization.
Gene name
ACSL6 (acyl-CoA synthetase long-chain family member 6)
None of the resulting chimeric transcripts, except for the ACSL6/ETV6 transcript in the RAEB case, led to a fusion protein.
Dna rna description
57,74 kb, 21 exons; alternate splicing
Protein description
Two splicing isoforms, a long and a short. The gene encodes an AMP binding enzyme; plays an important role in fatty acid metabolism in brain, responsible for activation of long-chain fatty acids in erythrocytes. Wide expression, expression low at earlier stages of erythroid development but very high in reticulocytes.

Result of the Chromosomal Anomaly


A novel human gene, called ACS2 (acyl-CoA synthetase-2), was identified as an ETV6 fusion partner in a recurrent t(5;12)(q31;p13) translocation. Northern blot analysis detected high levels of ACS2 expression in brain, fetal liver, and bone marrow, and the gene was found to be highly conserved in man and rat. The ETV6/ACSL6 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACSL6 in the AEL patient, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACSL6 in the AML patient, and a short in-frame fusion of exon 1 of ETV6 to the 3-prime untranslated region of ACSL6 in the patient with RAEB. Reciprocal ACSL6/ETV6 transcripts were identified in 2 of the cases. FISH with ETV6 cosmids on 12p13, and BACs and PIs on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5-prime portion of the ACSL6 gene, and that the 5q31 breakpoint of the RAEB case involved the 3-prime portion of the ACSL6 gene. None of the resulting chimeric transcripts except for the ACSL6/ETV6 transcript in the RAEB case led to a fusion protein.
A case with a CML and a t(5;12)(q31;p13) was characterized, and 3 different ETV6/ACSL6 transcripts were detected. Moreover, as a consequence of the translocation IL-3/CSF2, located at 5q31, was ectopically expressed in the leukemic cells.

Highly cited references

Pubmed IDYearTitleCitations
274585502016Chronic eosinophilic leukemia, NOS with t(5;12)(q31;p13)/ETV6-ACSL6 gene fusion: a novel variant of myeloid proliferative neoplasm with eosinophilia.7
165722022006t(5;12)(q23-31;p13) with ETV6-ACSL6 gene fusion in polycythemia vera.6
277468192016Myeloid Neoplasms with t(5;12) and ETV6-ACSL6 Gene Fusion, Potential Mimickers of Myeloid Neoplasm with PDGFRB Rearrangement: Case Report with Imatinib Therapy and Review of the Literature.1
349793552022t(5;12)(q31;p13)/ETV6::ACSL6 and t(6;9)(p23;q34)/DEK::NUP214 concurrence in acute myeloid leukemia: an unusual association of two rare abnormalities.0
327233652020ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes.0


Pubmed IDLast YearTitleAuthors
118612952002Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13).Cools J et al
165722022006t(5;12)(q23-31;p13) with ETV6-ACSL6 gene fusion in polycythemia vera.Murati A et al
105023161999Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).Yagasaki F et al


Fusion gene

ETV6/ACSL6 ETV6 (12p13.2) ACSL6 (5q31.1) M t(5;12)(q31;p13)|ETV6/ACSL6 ETV6 (12p13.2) ACSL6 (5q31.1) TIC
Atlas Image
t(5;12)(q31;p13) G- banding - left: Courtesy Melanie Zenger and Claudia Haferlach; middle and right: Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap,UW Cytogenetic Services.


Maria D. Odero

t(5;12)(q31;p13) ETV6/ACSL6 in MDS,AML and AEL

Atlas Genet Cytogenet Oncol Haematol. 2007-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1344/t(5;12)(q31;p13)-etv6-acsl6-in-mds-aml-and-ael