t(8;14)(q24;q11) TRA/MYC

2001-04-01   Jacques Boyer  

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology

Disease

acute lymphoblastic leukemia (ALL), (rare lymphoblastic lymphoma)

Phenotype stem cell origin

T lineage ( TCR alpha beta + or TCR gamma delta ). May be early-B lineage : conceivably the rare cases with early-B lineage represent a bipotential B-T lineage.

Epidemiology

rare: prevalence 0.5 to 1.3 % among all cases off ALL and about 2% among T ALL; male predominance; median age 5 years

Clinics

bulky extramedullary leukemia, central nervous system (CNS) infiltration

Cytology

high white blood cell count

Prognosis

the disease progress rapidly and response to conventional therapy is poor, median survival 11 months

Genes Involved and Proteins

Note
on the molecular point of view the proto oncogen c-myc is juxtaposed with the gene of the T-cell receptor alpha chain (TCR-alpha)
Gene name
MYC v-myc myelocytomatosis viral oncogene homolog (avian)
Location
8q24.21
Dna rna description
c-myc has three exons, two promoters P1 and P2 control the c-myc transcription
Protein description
Myc protein is a transcription factor of the helix loop leucin zipper family that activates transcription as obligate heterodimer with a partner protein, Max
Gene name
TRA (T cell Receptor Alpha)
Location
14q11.2
Dna rna description
the TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments. The TCR alpha/delta locus is transcribed in a centromer to telomer direction.
Protein description
T-cell receptor
Gene name
TRD (T cell Receptor Delta)
Location
14q11.2
Dna rna description
the TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments. The TCR alpha/delta locus is transcribed in a centromer to telomer direction.
Protein description
T-cell receptor

Result of the Chromosomal Anomaly

Description

the majority of breakpoints are localised within the TCR delta gene although they may also involve TCR alpha J and rarely TCR alpha V. The 3 part of the TCR alpha gene is relocated downstream of the c-myc protooncogene. The c-myc oncogene is not structurally altered.

Transcript

detection of TCR alpha rearrangements is hampered by the large number of J segments

Note

no fusion protein but promoter exchange

Description

high levels of electrophoretically normal p64 and p67 c-myc proteins are detected and both products keep their instability. Preferential utilization of P2 is maintained.

Oncogenesis

the activation of the gene myc is likely to result from its juxtaposition to the enhancer element of the TCR alpha gene with stimulates constitutive synthesis of normal c-myc.

Article Bibliography

Pubmed IDLast YearTitleAuthors
86053271996Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique.
29669211988Molecular mechanisms of a t(8;14)(q24;q11) translocation juxtaposing c-myc and TcR-alpha genes in a T-cell leukaemia: involvement of a V alpha internal heptamer.Bernard O et al
14151751992A new case of acute lymphoblastic leukemia B-cell type with chromosomal rearrangements involving the T-cell receptor breakpoint at band 14q11.Cigudosa JC et al
34864701986Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias.Erikson J et al
23974751990Translocation between chromosomes 8q24 and 14q11 in T-cell acute lymphoblastic leukemia.Inaba T et al
21693361990Rearrangements in the human T-cell-receptor alpha-chain locus in patients with adult T-cell leukemia carrying translocations involving chromosome 14q11.Isobe M et al
14066581992Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation.Kasai M et al
13856381992Pediatric leukemia/lymphoma with t(8;14)(q24;q11).Lange BJ et al
34668701986A t(8;14)(q24;q11) translocation in a T-cell leukemia (L1-ALL) with c-myc and TcR-alpha chain locus rearrangements.Mathieu-Mahul D et al
35290891986Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3' side of MYC.McKeithan TW et al
25350341989An (8;14)(q24;q11) translocation involving the T-cell receptor alpha-chain gene and the MYC oncogene 3' region in a B-cell lymphoma.Park JK et al
13770081992Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.Secker-Walker LM et al
35178601986Gene encoding the alpha chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8;14 translocation in a cell line from a human T-cell leukemia.Shima EA et al
94087521997Molecular analysis of the t(8;14)(q24;q11) chromosomal breakpoint junctions in the T-cell leukemia line MOLT-16.Shima-Rich EA et al
17056371991c-myc gene expression in a leukemic T-cell line bearing a t(8;14) (q24;q11) translocation.Soudon J et al

Summary

Fusion gene

TRA/MYC TRA (-) MYC (8q24.21) M t(8;14)(q24;q11)
Atlas Image
t(8;14)(q24;q11) G-banding - courtesy Charles Bangs and Leena Borkar, and R-banding (right) - courtesy Jacques Boyer.

Citation

Jacques Boyer

t(8;14)(q24;q11) TRA/MYC

Atlas Genet Cytogenet Oncol Haematol. 2001-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1061/js/lib/gene-explorer/css/template-card.css