t(7;14)(p15;q11) TRD/HOXA10

2017-10-01   Adriana Zamecnikova  

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com
2.Laboratoire dHématologie, INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes, AP-HP, Paris, France
3.Laboratoire d Hématologie, INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes, AP-HP, Paris, France

Abstract

Review on t(7;14)(p15;q11) TRD/HOXA10, with data on clinics.

Clinics and Pathology

Disease

T-cell Acute lymphoblastic leukemia (T-ALL)

Phenotype stem cell origin

T lineage TCR gamma delta +, CD4/8 double positive (DP), CD1a- ; FAB L1 or L2. immunophenotype

Epidemiology

2 patients diagnosed with T-cell acute lymphoblastic leukemia: a 29-years old male (Asnafi et al., 2003) and a 9- years old male (Mahlow et al., 2015). In addition, 3 more cases with t(7;14)(p15;q11) have been described: a 51-years old male with mycosis fungoides/Sezary syndromeand TRA+ rearrangement (Santos et al., 1990), a 31-year old female with T-ALL (Garipidou et al., 1991) and a 46-years old female with refractory anemia with excess of blasts and rearranged HOXA9 (Chen et al., 2005) (Table 1).
Table 1. Reported cases with t(7;14)(p15;q11)
 Sex/AgeDiagnosisKaryotypeGenes involved
4F/46 RAEB 46,XX,t(7;14)(p15;q11),+8HOXA9/?
2F/31 T-ALL 46,XX,t(7;14)(p15;q11),add(18)(q23) ?
3M/29 T-ALL46,XY,t(7;14)(p15;q11),t(10;11)(p14;q21),add(18)(q23)HOXA-TRA/D
CALM-AF10
59/M T-ALL46,XY,del(6)(q14q21),t(7;14)(p15;q11.2),del(9)(p13)/92,idemx2 HOXA-TRA/D
1M/51Mycosis fungoides/ Sezary syndrome41-45,X,-Y,add(5)(q33),+7,t(7;14)(p15;q11),-8,-10,del(10)(p13), del(11)(q21q23),del(12)(p13),add(14)(q11),add(15)(q15),incTRA+, TRG+
)
1. Santos et al., 1990; 2. Garipidou et al., 1991; 3.Asnafi et al., 2003; 4. Chen et al., 2005; 5. Mahlow et al., 2015.Abbreviations: M: male; F: female; T-ALL: T-cell acute lymphoblastic leukemia, RAEB: refractory anemia with excess of blasts.

Cytogenetics

Atlas Image
Figure 1. FISH hybridization result using a TCRA/D distal (Green) and HOXA proximal (orange) FISH probes showing a fusion signal - Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf.

Cytogenetics molecular

Balanced t(7;14)
  • Der(7):Intronic region of HOXA locus on 7p15 between HOXA6 and HOXA7 genes fused with Jd1 segment of TCRD on 14q11.
  • Der(14): DREC segment on chromosome 14q11 rearranged with Dd2 and Dd3 segments and fused to the telomeric part of HOXA locus on 7p15
    • Atlas Image
    Figure 2. (A) Partial karyotypes showing t(7;14)(p15.2;q11.2). (B) Fluorescence in situ hybridization with LSI TCRA/D break apart probe (Vysis, Abbott Moleculars, US) showing TCRA/D rearrangement as a result of t(7;14)(p15.2;q11.2) - Courtesy Adriana Zamecnikova.

    Additional anomalies

    The case described by Asnafi et al. 2003 also expressed (by RQ-PCR) a CALM-AF10 fusion transcript (t(10;11)(p13;q14-21)). Associated with 6q and 9pdeletion in the other T-ALL case with fusion of HOXA-TCRA/D gene regions (Mahlow et al., 2015).

    Variants

    variant translocation cases are reported: 9 cases of T-ALLs having the HOXA locus translocated to TCRB in a t(7;7). The breakpoints on 7p15 in those HOXA-TCRB cases are more centromeric, close to HOXA9

    Genes Involved and Proteins

    Gene name
    HOXA@
    Location
    7p15
    Note
    HOXA6 and HOXA7 lie at 6,9kb from each other on 7p15
    Protein description
    various HOXA genes act as transcription factors playing important roles in the differentiation and commitment processes of embryonic and hematopoietic cells.
    Gene name
    TRD (T cell Receptor Delta)
    Location
    14q11.2
    Note
    Breakpoint on der(7) lie 5 from Jd1. Breakpoint on der(14)lies 12 nucleotides 5 of the 3 end of the DREC segment.
    Protein description
    Protein encoded by the TCRD locus are the T-cell receptor chains.

    Result of the Chromosomal Anomaly

    Atlas Image
    Figure 3. Sequence of events leading to the final translocation. Exons are represented by boxes. Triangles represent RSS and show their orientation. E=enhancer- Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf..
    Atlas Image
    Figure 4. The nucleotide sequence of both derivatives implicated in the t(7 ;14) translocation. Underscored are RSS or RSS-like sequence in the vincinity of the breakpoints. In lower case letters: non templated nucleotides at the junction- Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf..

    Description

    No fusion protein. Overexpression of HOXA genes as a result of the translocation with TCRD was expected, as it was demonstrated to be the case in HOXA-TCRB T-ALLs. However this case had a CALM-AF10 fusion in the same leukemic clone. CALM-AF10 is already known to be associated with HOXA cluster global overexpression. The HOXA pattern of expression in this case was similar to other CALM-AF10 T-ALL.

    Oncogenesis

    Probable, as several HOX/HOXA genes have been implicated in leukemic processes.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    117317952002MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.Armstrong SA et al
    150540412004Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy.Asnafi V et al
    126767842003CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.Asnafi V et al
    165722062006HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation.Bergeron J et al
    157590352005Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries.Chen B et al
    161078952005CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes.Dik WA et al
    18262291991The use of fluorodeoxyuridine synchronization for cytogenetic investigation of acute lymphoblastic leukemia.Garipidou V et al
    117813682002V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites.Marculescu R et al
    124534182002MLL targets SET domain methyltransferase activity to Hox gene promoters.Milne TA et al
    23404971990Possible correlation between a specific alteration t(7;14) and the rearrangement of TCR observed in a Sézary's syndrome.Santos M et al
    157746212005HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).Soulier J et al
    156744122005A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias.Speleman F et al

    Citation

    Adriana Zamecnikova

    t(7;14)(p15;q11) TRD/HOXA10

    Atlas Genet Cytogenet Oncol Haematol. 2017-10-01

    Online version: http://atlasgeneticsoncology.org/haematological/1435/gene-fusions-explorer/favicon/gene-explorer/teaching-explorer/

    Historical Card

    2006-06-01 t(7;14)(p15;q11) TRD/HOXA10 by  Julie Bergeron,Elizabeth Macintyre,Vahid Asnafi 

    Laboratoire dHématologie, INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes, AP-HP, Paris, France