t(7;14)(q35;q32.1) TRB/TCL1A
inv(14)(q11q32.1) TRA-TRD/TCL1A
t(14;14)(q11;q32.1) TRA-TRD/TCL1A

2018-06-01   Tatiana Gindina 

1.Raisa Gorbacheva Memorial Institute of Childrens Oncology, Hematology and Transplantation at First Pavlov St. Petersburg State Medical University, Saint-Petersburg, Russia
2.Laboratoire d hématologie, CH du MANS, France

Abstract

Review on t(7;14)(q35;q32), inv(14)(q11q32) and t(14;14)(q11;q32), with data on clinics, and the genes involved.

Clinics and Pathology

Disease

Ataxia telangiectasia (AT) ,  Angioimmunoblastic T-cell lymphoma.

Clinics

AT is a rare multisystem disease characterized by cerebellar ataxia, immunodeficiency, sensitivity to ionizing radiation, chromosome instability and predisposition to lymphoid malignancies, including T-PLL. , T-PLL main disease features at presentation are splenomegaly (79%), lymphadenopathy (46%), hepatomegaly (39%), skin lesion (23%), pleural effusion (15%) and marked lymphocytosis (> 100 X 109/L) (72%)

Cytogenetics

  • Spontaneous chromatid/chromosome breaks are found in this disease with a high frequency.
  • The best diagnosis test is on the highly elevated level (10% of mitoses) of inv(7), t(14;14)
  • Clonal rearrangement further occurs in 10% of patients, but without manifestation of malignancy: t(14;14), inv(14) or t(X;14)
  • The karyotype is often complex. Deletion of 6q, 13q, trisomy 3, trisomy 7 or partial trisomy of the long arm of chromosome 7 are frequently found. , Inv(14) is exceedingly rare in T cell acute lymphoblastic leukemia. In two cases reported , inv(14) coexists with other cytogenetic aberrations well described in T-ALL, like t(11;14)(p13;q11) and rearrangement at chromosome 7q34. , 
  • The variant t(X;14)(q28;q11) may be found. , Inv(14) is a exceedingly rare phenomenon in lymphoid malignancy of B lineage. It has been reported in a patient with B-cell chronic lymphocytic leukemia but only in a PHA stimulated bone marrow. Only two cases of lymphoblastic leukemia of B-lineage with inv(14) have been reported. These two cases are pre-B2 ALL (CD10+ and cytoplamic μ chain negative). , 
  • Anomalies of 11q23, where the ataxia teliangectasia mutated gene is located, have also been reported in T-PLL Anomalies of the short arm of chromosome 12 seem to be observed with a high frequency so as 13q14.3 deletions. , 
  • 55 to 80 % of cases have additional abnormality affecting the chromosome 8 : i(8)(q10) (43%) , t(8;8)(p12;q11) (14%), +8 (14%) and abnormality of the short arm of chromosome 8 (14%). Deletions at 12p13 and 22q and amplification of 5p are on FISH and/or SNP array (Hetet et al., 2000; Bug et al., 2009; Nowak et al., 2009). Abnormalities of chromosomes 6 (33%) and 17 (26%) have also been identified by karyotyping and CGH (Brito-Babapulle et al., 1991, Costa et al., 2003). The TP53 gene is deleted, with overexpression of p53, in some cases (Brito-Babapulle et al., 2000).
  • Disease

    Acute lymphoblastic leukemia (ALL) of T lineage.

    Note

    An inv(14)(q11q32.1) was found in about 80% cases of T-PLL. In 10%, there is t(14;14)(q11;q32.1) (Brito-Babapulle et al., 1991; Maljaei et al, 1998).

    Phenotype stem cell origin

    Mature post-thymic T-cell malignancy
  • CD4+CD8- (70%) CD4+CD8+ (25%) or CD4-CD8+ (<10%)
  • CD7+ bright and surface CD3 negative in 20% of cases.
  • Clinics

    T-PLL is rare and affects adults, occurs slightly more often in men at advanced age.

    Cytology

    In 70% of cases proliferation of medium-sized lymphocytes with either a regular or a irregular nuclear outline and one single nucleolus (or absent). The cytoplasme is scanty, agranular, deeply basophilic and often with protrusions (blebs).
    In 20% of cases there are no obvious differencies between B and T prolymphocytes with proeminent nucleolus.
    In rare cases T prolymphocytes show a polylobated nucleus or a cerebriform configuration (as sezary cell)

    Cytogenetics

  • inv(14)(q11q32) is the most frequent chromosomal abnormality and occurs in more than two thirds of cases.
  • Prognosis

    T-PLL has an aggressive clinical course in most patients with median survival times ranging from 7 to 30 months. Cases with a more chronic course have also been reported, but such cases may progress after 2-3 years (Durig qt al., 2007).

    Disease

    Adult T-cell leukemia/lymphoma.

    Note

    Inversion inv(14)(q11q32.1) and translocation t(14;14)(q11;q32.1) were reported in 10 and 2 cases, respectively (Miyamoto et al., 1984; Fujita et al., 1986; Sadamori et al., 1986; Sanada et al., 1987; Isobe et al., 1990; Sadamori et al., 1991; Kamada et al., 1992; Itoyama et al., 2001).

    Disease

    Leukemias of B lineage.

    Note

    The translocations (7;14)(q35;q32.1), t(14;14)(q11;q32.1) and inversion inv(14)(q11q32.1) were found in 2 cases for each anomaly (Cosimi et al., 1990; Schlegelberger et al., 1990; Leich et al., 2007).

    Cytogenetics

    Additional aberrations were trisomy 3, trisomy 7, i(7q), dup(7q).

    Note

    Only 2 cases with translocation t(7;14)(q35;q32.1) (Yabe et al., 2016; Yabe et al., 2016).

    Cytogenetics

    The translocation was as a sole aberration.

    Note

    The inversion inv(14)(q11q32.1) were observed in 2 cases (Brito-Babapulle et al., 1997).

    Cytogenetics

    Complex karyotype in both cases.

    Disease

    Acute myeloid leukemia with lymphoid associated antigens.

    Genes Involved and Proteins

    Gene name
    TCL1A (T-cell leukemia/lymphoma 1A).
    Location
    14q32.13.
    Note
    The TCL1A oncogene is located on chromosome 14q32.1. It belongs to the TCL1 family. TCL1A gene is 6.5 Kb in size and contains four exons.
  • TCL1B is located on 14q32.1 16 Kb centromeric of TCL1A and shows 60% similarity to TCL1A; TCL1A and TCL1B are located in the about 160 kb region of breakpoints observed in T-cell leukemia cases with translocations at 14q32.1.
  • Semi quantitative RT-PCR analysis revealed that both TCL1A and TCL1B genes are expressed in spleen, tonsil, fetal liver, fetal kidney and fetal thymus. However the TCL1B gene is expressed in a wide variety of tissues. Normally, TCL1A expression is observed in early T cell progenitors (CD4- CD8- CD3-) and lymphoid cell of the B lineage: pre B cells and immature IgM expressing B cells.
  • TCL1A, TCL1B encode for protein of about 14 kDa. TCL1A 14 kDa protein consists of an eight-stranded antiparallel beta barrel with a hydrophobic core and are predicted to bind small hydrophobic ligands such as retinoids, nucleosides or fatty acids.
  • NOTE: in addition to TCL1A and TCL1B the locus contains an additional TCL1- neighboring gene ( TCL6) encoding proteins of 141 and 110 amino acids (Saitou et al., 2000).
  • Gene name
    MTCP1 (Mature T Cell Proliferation 1)
    Location
    Xq28
    Dna rna description
    The MTCP1 is located at Xq28 and activated in rare cases of T-PLL with a t(X;14)(q28;q11) translocation. , 
  • The TCR delta locus contains three D segments and four J segments, whereas the TCR alpha J regions spans approximately 80 Kb and contains at least 61 segments. , 
  • The TCR alpha/delta locus is transcribed in a centromer to telomer direction. , 
  • The TCR delta locus contains three D segments and four J segments, whereas the TCR alpha J regions spans approximately 80 Kb and contains at least 61 segments. , 
  • The TCR alpha/delta locus is transcribed in a centromer to telomer direction.
  • Protein description
    MTCP1 encodes for two proteins p8MTCP1 and p13MTCP1
    Gene name
    TRA (T cell Receptor Alpha)
    Location
    14q11.2
    Dna rna description
  • The size of TCR alpha/delta locus is about 1 Mb. The TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments.
  • Protein description
    T-cell receptor
    Gene name
    TRD (T cell Receptor Delta)
    Location
    14q11.2
    Dna rna description
  • The size of TCR alpha/delta locus is about 1 Mb. The TCR delta variable (V) diversity (D) joining (J) and constant region genes are situated within the TCR alpha locus between the TCR alpha V and the TCR alpha J segments.
  • Protein description
    T-cell receptor

    Result of the Chromosomal Anomaly

    Description

  • TCL1A and TCL1B are expressed at very low level in normal bone marrow and peripheral lymphocytes but are activated in the T-PLL by juxtaposition to the T cell receptor alpha/delta locus at 14q11.
  • The another gene of TCL1 family, MTCP1 is activated in rare cases of T-PLL with a t(X;14) translocation and is also homologous to TCL1A gene.
  • Breakpoints at 14q32.1 involve a chromosomal segment of about 160 Kb and cluster in two regions. The centromeric region is mainly involved in inversions, whereas the telomeric region is involved in simple translocations.
  • Oncogenesis

    TCL1A has been shown to promote cell proliferation and survival by acting as a coactivator of the protein kinase B (AKT), a key intracellular survival regulator. The protein kinase AKT , the homologue of v-akt isolated from the retrovirus AKT8, which causes T-cell lymphomas in mice, is a key player in transduction of antiapoptotic and proliferative signals in T-cell. The TCL1 protein, encoded by the TCL1A oncogene, interacts with the AKT, this interaction results in the enhancement of the AKT kinase activity and promotes its nuclear transport. In contrast, AKT kinase does not interact with the TCL1B protein. The biological outcome of the TCL1A-induced enhancement of AKT activity is expected to occur through the phosphorylation of AKT specific targets. Because the TCL1A activated AKT translocates into the nucleus, the most likely targets are nuclear. Recent work revealed that the TCL1A oncoprotein also inhibits activation-induced cell death and growth arrest by inhibiting the proapoptotic PRKCG and ERK pathways (Despouy et al., 2007; Hsi et al., 2014).

    Bibliography

    Pubmed IDLast YearTitleAuthors
    90744121997Relationship of T leukaemias with cerebriform nuclei to T-prolymphocytic leukaemia: a cytogenetic analysis with in situ hybridization.Brito-Babapulle V et al
    194809372009Recurrent loss, but lack of mutations, of the SMARCB1 tumor suppressor gene in T-cell prolymphocytic leukemia with TCL1A-TCRAD juxtaposition.Bug S et al
    22841411990Rearrangements on chromosomes 7 and 14 with breakpoints at 7q35 and 14q11 in angioimmunoblastic lymphadenopathy and IBL-like T-cell lymphoma.Cosimi MF et al
    145807692003High levels of chromosomal imbalances in typical and small-cell variants of T-cell prolymphocytic leukemia.Costa D et al
    178462282007The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKCtheta and ERK pathways.Despouy G et al
    34855821986Recurrent chromosome abnormalities in adult T-cell lymphomas of peripheral T-cell origin.Fujita K et al
    119201682000Recurrent molecular deletion of the 12p13 region, centromeric to ETV6/TEL, in T-cell prolymphocytic leukemia.Hetet G et al
    253108352014T-cell prolymphocytic leukemia frequently shows cutaneous involvement and is associated with gains of MYC, loss of ATM, and TCL1A rearrangement.Hsi AC et al
    113696582001Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki.Itoyama T et al
    15409561992Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.Kamada N et al
    175822372007Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas.Leich E et al
    96149081998Abnormalities of chromosomes 8, 11, 14, and X in T-prolymphocytic leukemia studied by fluorescence in situ hybridization.Maljaei SH et al
    66114411984Chromosome abnormalities of leukemia cells in adult patients with T-cell leukemia.Miyamoto K et al
    192789632009Molecular allelokaryotyping of T-cell prolymphocytic leukemia cells with high density single nucleotide polymorphism arrays identifies novel common genomic lesions and acquired uniparental disomy.Nowak D et al
    16591011991Relationship between chromosomal breakpoint and molecular rearrangement of T-cell antigen receptors in adult T-cell leukaemia.Sadamori N et al
    28887141987Chromosomal abnormalities in non-Hodgkin lymphoma with peripheral T-cell type: effect of HTLV-I infection.Sanada I et al
    22938831990Inv(14)(q11q32) in one of four different clones in a case of angioimmunoblastic lymphadenopathy.Schlegelberger B et al

    Summary

    Atlas Image
    Left: inv(14)(q11q32)and i(8q), G- banding - Courtesy Jean Luc Lai; right: inv(14)(q11q32) and t(14)(14) with i(7q), G- banding - Courtesy Tatiana Gindina.

    Citation

    Tatiana Gindina

    t(7;14)(q35;q32.1) TRB/TCL1A
    inv(14)(q11q32.1) TRA-TRD/TCL1A
    t(14;14)(q11;q32.1) TRA-TRD/TCL1A

    Atlas Genet Cytogenet Oncol Haematol. 2018-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/2049/t(7;14)(q35;q32-1)-trb-tcl1a-br-inv(14)(q11q32-1)-tra-trd-tcl1a-br-t(14;14)(q11;q32-1)-tra-trd-tcl1a

    Historical Card

    2001-06-01 t(7;14)(q35;q32.1) TRB/TCL1A
    inv(14)(q11q32.1) TRA-TRD/TCL1A
    t(14;14)(q11;q32.1) TRA-TRD/TCL1A
     by  Jacques Boyer 

    Laboratoire d hématologie, CH du MANS, France

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