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

Written2007-05Berthold Streubel
Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1458
 
  t(5;9)(q33;q22) G-banding

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 / cell stem 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
Location 5q33
Dna / Rna centromere to telomere orientation; Exons: 17
Protein 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
Location 9q22
Dna / Rna centromere to telomere orientation; Exons: 13-14 (alternative spliced)
Protein 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

Hybrid gene
Description 5'ITK-3'SYK
Transcript N-terminal ITK (bp 1-577) fused in frame with C-terminal SYK cDNA (breakpoint bp 1063)
  
Fusion Protein
 
  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).
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

Leukocyte protein tyrosine kinases: potential targets for drug discovery.
Bolen JB, Brugge JS
Annual review of immunology. 1997 ; 15 : 371-404.
PMID 9143693
 
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, van Oers NS, Tran A, Turka L, Law CL, Ryan JC, Clark EA, Weiss A
Journal of immunology (Baltimore, Md. : 1950). 1994 ; 152 (10) : 4758-4766.
PMID 8176201
 
Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12).
Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towatari M, Tanimoto M, Saito H
Blood. 2001 ; 97 (4) : 1050-1055.
PMID 11159536
 
Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.
Liao XC, Littman DR
Immunity. 1995 ; 3 (6) : 757-769.
PMID 8777721
 
T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.
Liu KQ, Bunnell SC, Gurniak CB, Berg LJ
The Journal of experimental medicine. 1998 ; 187 (10) : 1721-1727.
PMID 9584150
 
Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.
Schaeffer EM, Debnath J, Yap G, McVicar D, Liao XC, Littman DR, Sher A, Varmus HE, Lenardo MJ, Schwartzberg PL
Science (New York, N.Y.). 1999 ; 284 (5414) : 638-641.
PMID 10213685
 
Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.
Streubel B, Vinatzer U, Willheim M, Raderer M, Chott A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (2) : 313-318.
PMID 16341044
 
TNF activates Syk protein tyrosine kinase leading to TNF-induced MAPK activation, NF-kappaB activation, and apoptosis.
Takada Y, Aggarwal BB
Journal of immunology (Baltimore, Md. : 1950). 2004 ; 173 (2) : 1066-1077.
PMID 15240695
 

Citation

This paper should be referenced as such :
Streubel, Berthold
t(5;9)(q33;q22)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):319-321.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0509q33q22ID1458.html


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes ITK SYK

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;9)(q33;q22) ITK/SYK

External links

arrayMap (UZH-SIB Zurich)ITK (5q33.3) SYK (9q22.2)

ITK (5q33.3) SYK (9q22.2)

ITK (5q33.3) SYK (9q22.2)

Mitelman databaset(5;9)(q33;q22) [Case List]    t(5;9)(q33;q22) [Association List] Mitelman database (CGAP - NCBI)
arrayMap[select an item]
 
Mitelman databaseITK/SYK [MCList]  ITK (5q33.3) SYK (9q22.2)
Mitelman databaseITK/SYK [MCList]  ITK (5q33.3) SYK (9q22.2)
TICdbITK/SYK  ITK (5q33.3) SYK (9q22.2)
 
Disease databaset(5;9)(q33;q22) ITK/SYK
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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