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inv(7)(p15q34) TRB::HOXA10

t(7;7)(p15;q34) TRB::HOXA10

Written2005-10Barbara Cauwelier, Nicole Dastugue, Anne Hagemeijer, Frank Speleman
Génétique des Hémopathies, Laboratoire d'Hématologie, Hpital Purpan, 31000, Toulouse Cedex, France (ND)

(Note : for Links provided by Atlas : click)


ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1384

Clinics and Pathology

Disease T cell acute lymphoblastic leukemia (T-ALL) and non-Hodgkin lymphoma (T-NHL)
Phenotype / cell stem origin T lineage; occurs at early stage of T cell development (CD2-, CD4+, CD8-)
Epidemiology 3.5 % of T-ALL or T-NHL
Clinics hepato and/or splenomegaly, lymphadenopathy, mediastinal mass, moderate WBC count (15 to 100 X 109/l)
Cytology FAB L1 or L2


Cytogenetics Morphological This rearrangement remains undetected in poor quality metaphases. In less condensed, well banded metaphases, the abnormality may be suspected as del(7)(p15) or clearly as an inv(7)(p15q34).
  inv (7)(p15q34) G- banding (left) and R- banding (right)
Cytogenetics Molecular inv(7)(p15q34) and t(7;7)(p15;q34) can be detected by FISH using either TRB and HOXA flanking probes which gives a split signal of both probes in these cases. A fusion signal will be detected when combining the proximal TCR/distal HOXA flanking or the distal TCR/proximal HOXA flanking FISH probe.
  FISH results of inv(7)(Fig.1a and b) and t(7;7)(Fig.1c and d) case using TRB flanking (Fig.1a and 1c) and HOXA (Fig.1b and 1d) flanking probes
Additional anomalies most patients show no additional karyotypic abnormalities

Genes involved and Proteins

Note Chromosomal disruption of the HOXA gene cluster (7p15) following chromosomal rearrangement, leads to upregulation of HOXA gene expression, which are normally weakly expressed in T-ALL. Further studies are needed to determine the various patterns of HOXA gene upregulation but from present data, HOXA10 seems most consistently involved in keeping with the breakpoint position near HOXA9. The upregulation of HOXA10 expression is thought to result from enhancers embedded within the TRB locus, which is translocated upstream from these genes. Upregulation of HOXA genes has also been described for other subgroups of T-ALL i.e. the CALM-AF10 and MLL rearranged T-ALLs indicating a more general role for HOXA genes in T-ALL development.
HOXA,together with HOXB, HOXC and HOXD, belongs to the class I homeobox genes and compromises 11 HOXA cluster genes : HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11, HOXA13. Given the breakpoint position 5¹ to HOXA10 and its consistent overexpression in all TRB-HOXA rearranged cases, we currently assume that this gene exerts a specific oncogenic effect in this subgroup of T-ALLs.
Gene NameHOXA10 (homeobox A10)
Location 7p15.2
Note DNA-binding transcription factor which regulates gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Two transcript variants encoding different isoforms have been found for this gene. HOXA10 expression is normally present in hematopoietic stem cells and developing T-cells with decreasing expression as T-cells mature.
Dna / Rna 2 transcripts :
  • transcript variant 1 (isoform a) : 2 exons, transcript 2618 bp, protein 393 amino-acids
  • transcript variant 2 (isoform b) : 2 exons, transcript 2241 bp, protein 94 amino-acids
  • Protein DNA binding, transcription factor activity
    Gene NameTRB (T cell Receptor Beta)
    Location 7q34
    Note The human TRB locus at 7q34 spans 620 kb and consists of 82-85 genes. Enhancer sequences have been characterized 5.5kb 3' from TRBC2.
    Protein Proteins encoded by the TRB locus are the T-cell receptor beta chains

    Result of the chromosomal anomaly

    Fusion Protein
    Description no fusion protein, but ectopic expression of HOXA10
    Oncogenesis Little is known about the target genes for HOXA10. Cyclin-dependent kinase inhibitor p21 (alias CDKN1A,CIP1,WAF1) was shown to be a transcriptional target of HOXA10 in differentiating myelomonocytic cells. However, a potential role of p21 in HOXA10 driven oncogenesis has not been proved so far. In vitro transfection experiments with HOXA9 and HOXA10 showed upregulation of several genes of the Wnt pathway (Wnt10b, Frizzled1, Frizzled5) which are essential in hematopoietic stem cell renewal.

    To be noted

    translocations involving the TRB genes frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, etc.), responsable of the Immunoglobulin and T cell receptor V-J and V-D-J rearrangements.

    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.


    p21 is a transcriptional target of HOXA10 in differentiating myelomonocytic cells.
    Bromleigh VC, Freedman LP
    Genes & development. 2000 ; 14 (20) : 2581-2586.
    PMID 11040212
    Activation of stem-cell specific genes by HOXA9 and HOXA10 homeodomain proteins in CD34+ human cord blood cells.
    Ferrell CM, Dorsam ST, Ohta H, Humphries RK, Derynck MK, Haqq C, Largman C, Lawrence HJ
    Stem cells (Dayton, Ohio). 2005 ; 23 (5) : 644-655.
    PMID 15849172
    HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).
    Soulier J, Clappier E, Cayuela JM, Regnault A, García-Peydró M, Dombret H, Baruchel A, Toribio ML, Sigaux F
    Blood. 2005 ; 106 (1) : 274-286.
    PMID 15774621
    A 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, Cauwelier B, Dastugue N, Cools J, Verhasselt B, Poppe B, Van Roy N, Vandesompele J, Graux C, Uyttebroeck A, Boogaerts M, De Moerloose B, Benoit Y, Selleslag D, Billiet J, Robert A, Huguet F, Vandenberghe P, De Paepe A, Marynen P, Hagemeijer A
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (3) : 358-366.
    PMID 15674412
    Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development.
    Taghon T, Thys K, De Smedt M, Weerkamp F, Staal FJ, Plum J, Leclercq G
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (6) : 1157-1163.
    PMID 12764384


    This paper should be referenced as such :
    Cauwelier, B ; Dastugue, N ; Hagemeijer, A ; Speleman, F
    inv(7)(p15q34) - t(7;7)(p15;q34)
    Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):120-122.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

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

    Genes HOXA11 MIR196B

    Translocations implicated (Data extracted from papers in the Atlas)

     inv(7)(p15q34) TRB/HOXA10
     t(7;7)(p15;q34) TRB/HOXA10

    External links

    TRB (-) HOXA10 (7p15.2)

    TRB (-) HOXA10 (7p15.2)

    Mitelman databaseinv(7)(p15q34)
    Mitelman databaset(7;7)(p15;q34)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Mitelman databaseTRB::HOXA10 [MCList]  TRB (-) HOXA10 (7p15.2)
    Mitelman databaseTRB::HOXA10 [MCList]  TRB (-) HOXA10 (7p15.2)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed

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    indexed on : Fri Oct 8 16:36:48 CEST 2021

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