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HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation

Leukemia volume 20, pages 1184–1187 (2006)Cite this article

Recognized T-cell acute lymphoblastic leukemias (T-ALLs) oncogenic pathways include transcriptional deregulation of oncogenes by juxtapositioning to the T-cell receptor β (TCRB) or α/δ (TCRA/D) enhancer loci, resulting in overexpression of genes such as LMO2, LMO1, LYL1, TAL1/SCL, and homeodomain genes such as TLX1/HOX11, TLX3/HOX11L2 or HOXA. A V(D)J error-type mechanism has been proposed to explain such recurrent chromosomal events but other processes are likely to intervene, particularly those mediating the chromosomal break at the locus bearing the proto-oncogene.1 Evidence in favor of V(D)J-mediated errors include the presence of non-templated nucleotides (n-diversity) at the chromosomal junction and of recognition signal sequences (RSS) or RSS-like sequences at the vicinity of the breakpoints on the derivative chromosomes, although putative RSS-like sequences are usually incomplete.

The HOXA gene cluster on chromosome 7p15 has recently been described as a new recurrent TCRB partner in T-ALL.2, 3 In cases with TCRB-HOXA translocation, a variable but consistent combination of individual HOXA genes on both sides of the breakpoint appears to be upregulated. The juxtapositioning of TCRB enhancer elements and the HOXA locus disruption in itself might deregulate the whole cluster expression. In other cases, trans-regulating factors can deregulate the whole HOXA cluster. The MLL protein directly regulates HOX family genes4 and chimeric MLL oncoproteins are recognized to mediate HOX deregulation in AML and B- and T-lineage ALL.5 T-cell acute lymphoblastic leukemia with CALM-AF10 fusions also demonstrate HOXA cluster upregulation,2, 6 but the mechanisms mediating gene deregulation in these cases remain to be explored.

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Acknowledgements

This work was supported by the Fondation contre la leucémie de la Fondation de France and Association de Recherche sur le Cancer (ARC).

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  1. J Bergeron: J Bergeron is a Research Fellow of The Terry Fox Foundation through an award from the Natianal Cancer Institute of Canada

Authors and Affiliations

  1. Laboratoire d'Hématologie and INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes, AP-HP, Paris, France

    J Bergeron, C Millien, E Delabesse, K Beldjord, E Macintyre & V Asnafi

  2. Hematology Laboratory and INSERM U728, Institut Universitaire d'Hématologie, Hôpital Saint-Louis and Paris 7 University, Paris, France

    E Clappier & J Soulier

  3. Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium

    B Cauwelier & F Speleman

  4. Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France

    N Dastugue

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Bergeron, J., Clappier, E., Cauwelier, B. et al. HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation. Leukemia 20, 1184–1187 (2006). https://doi.org/10.1038/sj.leu.2404187

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