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t(7;19)(q34;p13) TRB/LYL1

Written2003-01Jacques Boyer
Laboratoire d' hématologie, CH du MANS, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1060
Note Non random translocations involving the short arm of chromosome 19 are observed in acute leukemia. The 19p13 genes E2A and LYL1 (see below) lie at two different translocation breakpoints in acute lymphoblastic leukemia. For instance the E2A gene is involved in the t(1;19)(q23 ;p13) in acute pre-B leukemia (B-ALL) and the LYL1 gene is structurally altered in the t(7;19)(q34 ;p13) in T cell leukemia (T-ALL).

Clinics and Pathology

Disease Specifically associated with T-cell Acute lymphoblastic leukemia (T-ALL)
Phenotype / cell stem origin Recents works, using oligonucleotide microarrays, show that several gene expression signatures are indicative of leukemic arrest at specific stages of normal thymocyte development :
  • LYL1 signature : pro-T (CD34+ CD3- CD4- CD8- CD1a-)
  • HOX11 : early cortical thymocyte and TAL1 late cortical thymocyte.
  • LYL1 positivity is related to higher expression levels of the MYCN, LMO2 and PLZF proto-oncogenes as well as the antiapoptotic gene BCL2. These findings have clinical importance (see Prognosis)
  • Epidemiology Rare : < 1% among T-ALL. The t(7;9)(q34;q32) is present in one case of a serie of 5 patients with 7q34 involvment.
    Prognosis HOX11 activation is significantly associated with a favorable prognosis, while expression of TAL1, LYL1 and surprisingly HOX11L2 confers a much worse response to treatment. The upregulation of BCL2 may explain their relative resistance to chemotherapy.

    Cytogenetics

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

    Genes involved and Proteins

    Gene NameTRB (T cell Receptor Beta)
    Location 7q34
    Dna / Rna 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.
    Protein T cell receptor beta chains.
    Gene NameLYL1 (lymphoblastic leukemia derived sequence 1)
    Location 19p13.2
    Note The LYL1 gene is assigned to 19p13.2-p13.1 by fluorescence in situ hybridation.
    Dna / Rna An RNA of about 1.5 kb is transcribed from this gene in a wide variety of lymphoid cell lines with the notable exception of thymocytes and T cells.
    Protein LYL1 encodes a basic helix-loop-helix (bHLH) phosphoprotein (size 108 amino acids) that is highly. Related to TAL1 : TAL1 and LYL1 HLH proteins show an 87% level of aminoacid identity.

    Result of the chromosomal anomaly

    Hybrid gene
    Description The LYL1 gene is structurally altered following the t(7;19) translocation, resulting in its head-to-head juxtaposition with the T cell receptor beta gene. In the human T cell line SUP-T7 established from an acute lymphoblastic leukemia, nucleotide sequence analysis showed that the point of crossover on chromosome 7 occured immediately adjacent to joining segment beta 1.1 within the TCR beta gene, suggesting that this translocation resulted from an error in TCR gene rearrangement. The t(7;19) resulted in truncation of the LYL1 gene and production of abnormal-sized RNAs suggesting a role for LYL1 in the pathogenesis of T Leukemia.
      
    Fusion Protein
    Oncogenesis Several helix-loop-helix (HLH) proteins are proposed to function as transcriptionnal regulatory factors based on their ability to bind in vitro the E-box motif of transcriptional enhancers. The enhancer binding HLH proteins include E47 and E12, two distinct but related polypeptides encoded by E2A gene that are able to form heterologous complexes with other HLH proteins like TAL1 and LYL1 polypeptides.
    Thus LYL1 may function as a dominant-negative mutant preventing the activation of E2A responsive genes. It is plausible that the inactivation of E2A target genes is an essential and common step toward the development of a number of T-cell malignancies.
    LYL1 interacts also with p105 the precursor of NF-KappaB1 p50. Biochemical studies indicate that this interaction is mediated by the HLH motif of LYL1 and the ankyrin-like motifs of p105.
    Ectopic expression of LYL1 cause a significant decrease in NF-KappaB- dependant transcription associated with a reduced level of NF-KappaB-dependant proteins.
      

    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

    Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Groupe Français de Cytogénétique Hématologique (GFCH).
    Blood. 1996 ; 87 (8) : 3135-3142.
    PMID 8605327
     
    TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia.
    Baer R
    Seminars in cancer biology. 1993 ; 4 (6) : 341-347.
    PMID 8142619
     
    E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas.
    Bain G, Engel I, Robanus Maandag EC, te Riele HP, Voland JR, Sharp LL, Chun J, Huey B, Pinkel D, Murre C
    Molecular and cellular biology. 1997 ; 17 (8) : 4782-4791.
    PMID 9234734
     
    Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.
    Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT
    Cancer cell. 2002 ; 1 (1) : 75-87.
    PMID 12086890
     
    Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105.
    Ferrier R, Nougarede R, Doucet S, Kahn-Perles B, Imbert J, Mathieu-Mahul D
    Oncogene. 1999 ; 18 (4) : 995-1005.
    PMID 10023675
     
    lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif.
    Mellentin JD, Smith SD, Cleary ML
    Cell. 1989 ; 58 (1) : 77-83.
    PMID 2752424
     
    Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells.
    Miyamoto A, Cui X, Naumovski L, Cleary ML
    Molecular and cellular biology. 1996 ; 16 (5) : 2394-2401.
    PMID 8628307
     
    Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.
    Secker-Walker LM, Campana D, Hawkins JM, Sampson RE, Coustan-Smith E
    Genes, chromosomes & cancer. 1992 ; 4 (1) : 41-45.
    PMID 1377008
     
    Clinical and biologic characterization of T-cell neoplasias with rearrangements of chromosome 7 band q34.
    Smith SD, Morgan R, Gemmell R, Amylon MD, Link MP, Linker C, Hecht BK, Warnke R, Glader BE, Hecht F
    Blood. 1988 ; 71 (2) : 395-402.
    PMID 2962650
     
    Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.
    Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A, Copeland A, de Jong P, Mohrenweiser H, Olsen A, Carrano A
    Genomics. 1993 ; 15 (1) : 133-145.
    PMID 8432525
     

    Citation

    This paper should be referenced as such :
    Boyer, J
    t(7;19)(q34;p13)
    Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):108-109.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t0719q34p13ID1060.html


    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes LYL1

    Translocations implicated (Data extracted from papers in the Atlas)

     t(7;19)(q34;p13) TRB/LYL1

    External links

    TRB (-) LYL1 (19p13.2)

    Mitelman databaset(7;19)(q34;p13) [Case List]    t(7;19)(q34;p13) [Association List] Mitelman database (CGAP - NCBI)
    arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
    Mitelman databaseTRB/LYL1 [MCList]  TRB (-) LYL1 (19p13.2)
     
    Disease databaset(7;19)(q34;p13) TRB/LYL1
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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