t(5;9)(q33;q22) ITK/SYK

2007-05-01   Berthold Streubel 

1.Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria

Clinics and Pathology

Disease

ITK-SYK transcripts were detected in 5 of 30 (17%) unspecified peripheral T-cell lymphomas, but not in cases of angioimmunoblastic T-cell lymphoma (n=9) and ALK-negative anaplastic large cell lymphoma (n=7).

Phenotype stem cell origin

The majority of t(5;9)(q33;q22)+ unspecified peripheral T-cell lymphomas share a very similar histological pattern with predominant involvement of lymphoid follicles and the same CD3+CD5+CD4+bcl-6+CD10+ immunophenotype.

Cytogenetics

Atlas Image
Colocalized fusion signals on the der(5) and der(9) confirm ITK-SYK rearrangement

Genes Involved and Proteins

Gene name
ITK (IL2-inducible T-cell kinase)
Location
5q33.3
Dna rna description
centromere to telomere orientation; Exons: 17
Protein description
The Tec family tyrosine kinase Itk has become increasingly recognized for its important role in regulating T-helper-cell differentiation. ITK is not required for Th2 differentiation per se, but effector Th2 cytokine production during recall responses is severely impaired in the absence of ITK.
Gene name
SYK (spleen tyrosine kinase)
Location
9q22.2
Dna rna description
centromere to telomere orientation; Exons: 13-14 (alternative spliced)
Protein description
SYK is a nonreceptor protein kinase that serves as a key regulator of multiple biochemical signal transduction events and has high homology to ZAP70 protein tyrosine kinase. In contrast to ITK, a translocation of SYK has been observed in hematopoietic neoplasia. Syk is expressed in a wide variety of hematopoietic cells but only in low levels in peripheral T-cells. Treatment of human Jurkat T-cells with the proapoptotic and inflammatory cytokine TNF activates SYK which consequently plays an essential role in TNF-induced activation of JNK, p38 MAPK, p44/p42 MAPK, NF- B, and apoptosis.

Result of the Chromosomal Anomaly

Description

5ITK-3SYK

Transcript

N-terminal ITK (bp 1-577) fused in frame with C-terminal SYK cDNA (breakpoint bp 1063)
Atlas Image
In frame fusion of N-terminal ITK to C-terminal SYK. The individual domains of Itk are indicated PH (pleckstrin homology), TH (proline-rich Tec homology), SH3 (Src homology), SH2 (Src homology), TK (tyrosine kinase) and of SYK N-terminal and C-terminal SH2 (Src homology), and TK (tyrosine kinase).

Bibliography

Pubmed IDLast YearTitleAuthors
91436931997Leukocyte protein tyrosine kinases: potential targets for drug discovery.Bolen JB et al
81762011994Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling.Chan AC et al
111595362001Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12).Kuno Y et al
87777211995Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.Liao XC et al
95841501998T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.Liu KQ et al
102136851999Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.Schaeffer EM et al
163410442006Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.Streubel B et al
152406952004TNF activates Syk protein tyrosine kinase leading to TNF-induced MAPK activation, NF-kappaB activation, and apoptosis.Takada Y et al

Summary

Fusion gene

ITK/SYK ITK (5q33.3) SYK (9q22.2) M|ITK/SYK ITK (5q33.3) SYK (9q22.2) M t(5;9)(q33;q22)|ITK/SYK ITK (5q33.3) SYK (9q22.2) TIC
Atlas Image
t(5;9)(q33;q22) G-banding

Citation

Berthold Streubel

t(5;9)(q33;q22) ITK/SYK

Atlas Genet Cytogenet Oncol Haematol. 2007-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1458/t(5;9)(q33;q22)

External Links