| Written | 2003-01 | Jacques Boyer |
| Laboratoire d' hématologie, CH du MANS, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9837/3 T lymphoblastic leukaemia/lymphoma |
| Atlas_Id | 1055 |
| Clinics and Pathology |
| Disease | Specifically associated with T-cell Acute Lymphoblastic Leukemia (T-ALL). |
| Note | This translocation is related to Notch1 (TAN1) dysregulation. Mutation or chromosomal rearrangements of Notch gene have not yet been identified outside of T-ALL but Notch1 was recently studied by immunohistochemistry in various subsets of human lymphomas. Strong staining was found in Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL) but much additional works is needed to determine whether Notch signaling is necessary for HL and ALCL growth and survival. |
| Phenotype / cell stem origin | T lineage. CD4+ CD8+ double positive stage. |
| Epidemiology | Rare: < 1% among T-ALL. |
| Cytogenetics |
| Cytogenetics Morphological | 9q34 is a partner of 7q34. The other partners are 1p34, 1p32, 9q32, 10q24, 11p13, 15q22, 19p13 |
| Additional anomalies | In T- lymphoblastic cell lines: polyploidy, inv(2)(p22;q11), inv(14)(q11;q32), del(6)(q23q27), del(4)(q13q35) |
| Genes involved and Proteins |
| Gene Name | TRB (T cell Receptor Beta) |
| Location | 7q34 |
| Dna / Rna | The TRB locus 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. A portion of the TCRB locus has been duplicated and translocated to the chromosome 9 at 9p21. |
| Protein | T cell receptor beta chains. |
| Gene Name | NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)) |
| Location | 9q34.3 |
| Note | Notch receptors are highly conserved transmembrane glycoproteins that regulate the morphogenesis through a signaling pathway with pleiotropic effects of apoptosis, proliferation and cellular differenciation. At least one Notch homolog is expressed in human bone marrow CD34+ cells, on the basis of this finding, it is likely that members of Notch family, including TAN1, may be involved in mediating cell-fate decisions during hematopoiesis. |
| Dna / Rna | DNA size: 49715 bases |
| Protein | Size: 2256 amino acids, 272550 Da. Functions as a receptor for membrane-bound ligands Jagged1. |
| Result of the chromosomal anomaly |
| Description | The t(7;9) disrupts the Notch1 gene, fusing the 3¹end portion encoding its intracellular domain (ICN) to enhancer and promoter elements of the T cell receptor (TCRB). This results in overexpression of a constitutively active form of Notch activating genes that inhibit cell differenciation.The t(7;9)(q34;q34) results in a serie of tumor specific 5¹deleted Notch1 mRNA transcripts. All known beakpoints fall within a single intron in the coding sequence for the EGF repeat 34 of Notch1. The t(7 ;9) truncated transcripts encode ICN1-like polypetides (ICN = intracellular portion of Notch receptor). These polypeptides localize to the nucleus and structurally resemble ICN1. The intracellular portion of Notch1 contains six ankyrin repeats that are similar to those found in cytoplasmic I kappa B proteins or I kappa B are specific inhibitors of nuclear factor NFKappa B transcription factors. |
| Oncogenesis | On primary effect of constitutive Notch 1 activation is the maturation arest of T lymphoblastes at the CD4+ CD8+ double positive stage but recent works suggest that Notch contributes to T cell transformation by influencing proliferation and survival, rather than merely blocking differenciation. |
| 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 |
| Notch signaling in cancer. |
| Allenspach EJ, Maillard I, Aster JC, Pear WS |
| Cancer biology & therapy. 2002 ; 1 (5) : 466-476. |
| PMID 12496471 |
| Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1. |
| Aster JC, Xu L, Karnell FG, Patriub V, Pui JC, Pear WS |
| Molecular and cellular biology. 2000 ; 20 (20) : 7505-7515. |
| PMID 11003647 |
| TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. |
| Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J |
| Cell. 1991 ; 66 (4) : 649-661. |
| PMID 1831692 |
| 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 |
| T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells. |
| Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T |
| The Journal of experimental medicine. 1996 ; 183 (5) : 2025-2032. |
| PMID 8642313 |
| Neoplastic transformation by Notch requires nuclear localization. |
| Jeffries S, Capobianco AJ |
| Molecular and cellular biology. 2000 ; 20 (11) : 3928-3941. |
| PMID 10805736 |
| A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors. |
| Milner LA, Kopan R, Martin DI, Bernstein ID |
| Blood. 1994 ; 83 (8) : 2057-2062. |
| PMID 7512837 |
| 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 |
| Citation |
| This paper should be referenced as such : |
| Boyer, J |
| t(7;9)(q34;q34) |
| Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):106-107. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0709q34q34ID1055.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | NOTCH1 | TRB |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(7;9)(q34;q34) TRB/NOTCH1 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Oct 12 18:21:14 CEST 2018 |
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