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


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.


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)
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)
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




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).

Highly cited references

Pubmed IDYearTitleCitations
163410442006Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.75
204395412010The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.56
272977922016Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma.48
206709542010The ITK-SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice mimicking human disease.27
240767792013ITK/SYK translocation in angioimmunoblastic T-cell lymphoma.17
215182552011TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK.16
253372572014Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene.11
195353342009The lymphoma-associated fusion tyrosine kinase ITK-SYK requires pleckstrin homology domain-mediated membrane localization for activation and cellular transformation.10
292795492017Recent Progress in the Understanding of Angioimmunoblastic T-cell Lymphoma.9
224098202012New biomarkers in T-cell lymphomas.9
243762682014Premature terminal differentiation protects from deregulated lymphocyte activation by ITK-Syk.8
232930252013Signaling 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 ZAP70.8
251482222014Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice.4
204395382010Peripheral T cell lymphoma: new model + new insight.4
198500082009Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein.4
341476952021Detection of Gene Fusion Transcripts in Peripheral T-Cell Lymphoma Using a Multiplexed Targeted Sequencing Assay.3
302174472018Translocation-generated ITK-FER and ITK-SYK fusions induce STAT3 phosphorylation and CD69 expression.3
214293562011[Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases].0


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


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


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)