t(5;9)(q33;q22) ITK/SYK
2007-05-01 Berthold Streubel Affiliation1.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
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)
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).
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 29279549 | 2017 | Recent Progress in the Understanding of Angioimmunoblastic T-cell Lymphoma. | 104 |
| 27297792 | 2016 | Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma. | 89 |
| 36845713 | 2023 | Tyrosine kinases in nodal peripheral T-cell lymphomas. | 73 |
| 25148222 | 2014 | Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice. | 59 |
| 19535334 | 2009 | The lymphoma-associated fusion tyrosine kinase ITK-SYK requires pleckstrin homology domain-mediated membrane localization for activation and cellular transformation. | 58 |
| 39755731 | 2025 | Differential regulatory effects of the N-terminal region in SYK-fusion kinases reveal unique activation-inducible nuclear translocation of ITK-SYK. | 51 |
| 31545408 | 2019 | Genome profiling revealed the activation of IL2RG/JAK3/STAT5 in peripheral T‑cell lymphoma expressing the ITK‑SYK fusion gene. | 51 |
| 23293025 | 2013 | Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70. | 38 |
| 20439541 | 2010 | The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma. | 33 |
| 25337257 | 2014 | Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene. | 29 |
| 20439538 | 2010 | Peripheral T cell lymphoma: new model + new insight. | 20 |
| 30217447 | 2018 | Translocation-generated ITK-FER and ITK-SYK fusions induce STAT3 phosphorylation and CD69 expression. | 0 |
| 21518255 | 2011 | TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK. | 0 |
| 36696631 | 2023 | Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms. | 0 |
| 22409820 | 2012 | New biomarkers in T-cell lymphomas. | 0 |
| 20670954 | 2010 | The ITK-SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice mimicking human disease. | 0 |
| 24376268 | 2014 | Premature terminal differentiation protects from deregulated lymphocyte activation by ITK-Syk. | 0 |
| 24076779 | 2013 | ITK/SYK translocation in angioimmunoblastic T-cell lymphoma. | 0 |
| 16341044 | 2006 | Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. | 0 |
| 19850008 | 2009 | Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein. | 0 |
| 34147695 | 2021 | Detection of Gene Fusion Transcripts in Peripheral T-Cell Lymphoma Using a Multiplexed Targeted Sequencing Assay. | 0 |
| 21429356 | 2011 | [Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases]. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9143693 | 1997 | Leukocyte protein tyrosine kinases: potential targets for drug discovery. | Bolen JB et al |
| 8176201 | 1994 | Differential 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 |
| 11159536 | 2001 | Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). | Kuno Y et al |
| 8777721 | 1995 | Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. | Liao XC et al |
| 9584150 | 1998 | T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. | Liu KQ et al |
| 10213685 | 1999 | Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. | Schaeffer EM et al |
| 16341044 | 2006 | Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. | Streubel B et al |
| 15240695 | 2004 | TNF 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
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
