t(7;9)(q34;q32) TRB/TAL2

2002-11-01   Jacques Boyer 

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology

Disease

Specifically associated with T-cell Acute lymphoblastic leukemia (T-ALL)

Epidemiology

The t(7;9)(q34;q32) is present in two cases of a serie of 5 patients with 7q34 involvment.

Clinics

Children with large mediastinal mass

Cytology

The hematological feature of the T-ALL with rearrangement of 7q34 shows high WBC (range 95 to 400 x 109/L)

Cytogenetics

Cytogenetics morphological

9q32 is a partner of 7q34. The other partners are 1p34,1p32, 9q34,10q24,11p13, 15q22 and 19p13

Additional anomalies

del(6)(q21), del(4)(q31q35)

Genes Involved and Proteins

Gene name
TRB (T cell Receptor Beta)
Location
7q34
Dna rna description
The TRB locus at 7q35 spans 685 Kb The locus contains 2 types of coding elements : TCR elements (64-67 variable genes TRBV, 2 clusters of diversity, joining and constant segments) and 8 trypsinogen genes. A portion of the TCRB locus has been duplicated and translocated to the chromosome 9 at 9p21.
Protein description
T cell receptor beta chains.
Gene name
TAL2 (T-cell acute lymphoblastic leukemia 2)
Location
9q31.2
Dna rna description
The TAL2 gene is located at q32
Protein description
TAL2 potentially encodes a basic helix-loop-helix (bHLH) phosphoprotein (size 108 amino acids) that is highly related to those specified by TAL1 and LYL1 also implicated in T-ALL. The bHLH protein interacts with the product of RBTN1 and RBTN2 (cysteine-rich LIM motifs)

Result of the Chromosomal Anomaly

Description

TAL2 is transcriptionaly activated by t(7;9)(q34;q32) in T-ALL.The chromosome 9 breakpoints of the t(7;9)(q34;q32) occur 33 kbp downstream of sequences that encode the TAL2 HLH domain. Translocated TAL2 are juxtaposed with transcriptional regulatory elements within the T-cell receptor beta-chain locus.

Note

No fusion protein.

Oncogenesis

The TAL2 transcription is activated ectopically in lymphoid cells and the inappropriate expression of TAL2 in these cells promotes development of T-ALL. Normaly, the TAL genes are not expressed in the thymus. The TAL genes become activated and expressed in the thymus upon chromosomal translocation which ultimately leads to the development of T-ALL.
The (7;9) translocation express a TAL2 gene product of 108 amino acids. In leukemic cells this product exists in both a phosphorylated and an unphosphorylated form. Serine residue 100 is the major site of TAL2 phosphorylation in vivo. And it serves as an effective in vitro substrate for MAP kinases such as ERK1.
TAL2 polypeptides interact in vivo with the E2A gene products to form HLH heterodimers that bind DNA, the result is the E2A inactivation. The E2A products are transcriptional factors implicated in the B and T cell development.
TAL2 product was also shown to bind with a GTP binding protein (DRG). The properties of TAL2 broadly resemble those described previously for TAL1 and therefore support the idea that both encoded proteins promote T-ALL by a common mechanism and the malignant potential of these proteins is likely to reside within their HLH domains though the inactivation of E2A.

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.
81426191993TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia.Baer R et al
92347341997E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas.Bain G et al
86497741996Association of a novel GTP binding protein, DRG, with TAL oncogenic proteins.Mahajan MA et al
13770081992Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.Secker-Walker LM et al
29626501988Clinical and biologic characterization of T-cell neoplasias with rearrangements of chromosome 7 band q34.Smith SD et al
79570521994Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia.Wadman I et al
17630561991TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia.Xia Y et al
81528051994Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA-binding activity.Xia Y et al

Summary

Fusion gene

TRB/TAL2 TRB (-) TAL2 (9q31.2) M t(7;9)(q34;q31)

Citation

Jacques Boyer

t(7;9)(q34;q32) TRB/TAL2

Atlas Genet Cytogenet Oncol Haematol. 2002-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1056/t(7;9)(q34;q32)