t(12;13)(p13;q14) LIN00598/ETV6

2007-11-01   Jean-Loup Huret 

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

Clinics and Pathology


Acute lymphoblastic leukemia (ALL) and myeloid malignancies.


This translocation is likely to be molecularly heterogeneous.


Only one case to date with identification of ETV6 and TTL as genes involved in the translocation : a 46 year-old male patient with ALL (blasts were CD10+/-, CD19+) (Qiao et al., 2003)..


Altogether, 15 cases are available:
Pre-B or early pre-B ALL cases, with an unbalanced sex ratio (7M/2F), and a median age of 6 years (range: 2-46), 7 of 9 patients being children (Raimondi et al., 1989; Pui et al., 1991; Raimondi et al., 1991; Chan et al., 1994; Kobayashi et al., 1994; Raimondi et al., 1997; Coignet et al., 1999; Qiao et al., 2003).
Myeloid cases: 1 chronic myelomonocytic leukaemia (CMML), 1 chronic myelogenous leukaemia in blast crisis (BC-CML), 1 M3 acute myeloid leukaemia (AML), 1 M0-AML, and 2 treatment related AML (t-AML). In contrast with lymphoid cases, the sex ratio was balanced (3M/3F), and median age was 58 years (range (51-70) (Zitzelsberger et al., 1990; Abeliovich et al., 1993; Fugazza et al., 1997; Tosi et al., 1998; Castro et al., 2000; Temperani et al., 2000).


The patient with ETV6/TTL hybrid gene attained complete remission, but relapsed and died of refractory disease 4 years after diagnosis.

Genes Involved and Proteins

ETV6 was found implicated in 4 ALL cases and 1 AML case; most other cases have been published before ETV6/TEL was known.
Gene name
ETV6 (ets variant 6)
Protein description
HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term. Transcriptional regulator; involved in bone marrow hematopoiesis.
Gene name
LINC00598 long intergenic non-protein coding RNA 598
Protein description
This gene/protein remains poorly known: there has been no study on it since the princeps paper by Qiao et al (2003).

Result of the Chromosomal Anomaly


Both reciprocal transcripts, TTL/ETV6 and ETV6/TTL, were detected. ETV6/TTL fusion transcript comprises 5 ETV6 exon 1, fused to TLL exon 9, resulting in a potential 31 amino acids peptid.
The other transcript, TTL/ETV6, comprises 5 TTL exons 1 to 5 or to 8a, fused to ETV6 from exon 2. The predicted 530 amino acids fusion protein consists mostly of ETV6 with both HLH and ETS domains, and could have modified transcriptional activities. On the other hand, a loss of function of ETV6 and/or of TTL could play the critical role in leukemogenesis.


Pubmed IDLast YearTitleAuthors
82425901993Therapy-related myelodysplastic syndrome. Two cytogenetically unrelated abnormal clones in a patient with multiple myeloma.Abeliovich D et al
107068862000Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms.Castro PD et al
79230601994Cytogenetics and immunophenotypes of childhood acute lymphoblastic leukemia in Hong Kong.Chan LC et al
103798681999Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.Coignet LJ et al
92345841997Duplication of the der(13)t(12;13)(p13;q14) in chronic myelomonocytic leukemia.Fugazza G et al
79677401994Clinical significance of chromosome abnormalities in childhood acute lymphoblastic leukemia in Japan.Kobayashi H et al
18785941991Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse.Pui CH et al
127643772003Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis.Qiao Y et al
9373267199712p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia.Raimondi SC et al
108671472000Late-appearing PML/RARalpha fusion transcript with coincidental t(12;13)(p13.2;q14) in acute promyelocytic leukemia lacking the t(15;17) cytogenetic anomaly.Temperani P et al
95231971998Identification of new partner chromosomes involved in fusions with the ETV6 (TEL) gene in hematologic malignancies.Tosi S et al
23576961990Cytogenetic and molecular analysis of a "masked" Philadelphia chromosome in chronic and blastic phases of chronic myeloid leukemia.Zitzelsberger H et al


Jean-Loup Huret

t(12;13)(p13;q14) LIN00598/ETV6

Atlas Genet Cytogenet Oncol Haematol. 2007-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1323/t(12;13)(p13;q14)