Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-01

AUTHORS

A D Paepe, A Hagemeijer, B Cauwelier, B D Moerloose, B Laurence, B Poppe, B Verhasselt, C Barin, C Chalas, C Charrin, C Gervais, C Graux, C Lefebvre, C Perot, C Terré, D Leroux, E Clappier, F Mugneret, F Sigaux, F Speleman, G Plessis, H Antoine-Poirel, H Cavé, I Luquet, J Cools, J Soulier, J Van den Akker, K D Keersmaecker, L Mauvieux, M J Mozzicconacci, M Lafage-Pochitaloff, M Lessard, M P Pagès, M-J Grégoire, N Dastugue, N Van Roy, P Cornillet-Lefebvre, P Heimann, P Jonveaux, R Berger, Y Benoit

ABSTRACT

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics. More... »

PAGES

121

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.leu.2404410

    DOI

    http://dx.doi.org/10.1038/sj.leu.2404410

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1024253494

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17039236


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