Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

• DOI: 10.1038/sj.leu.2404410
• Publication Date: 2006-10-12T15:38:33Z
• Authors: B Cauwelier; H Cavé; C Gervais; M Lessard; C Barin; C Perot; J Van den Akker; F Mugneret; C Charrin; M P Pagès; M-J Grégoire; P Jonveaux; M Lafage-Pochitaloff; M J Mozzicconacci; C Terré; I Luquet; P Cornillet-Lefebvre; B Laurence; G Plessis; C Lefebvre; D Leroux; H Antoine-Poirel; C Graux; L Mauvieux; P Heimann; C Chalas; E Clappier; B Verhasselt; Y Benoit; B D Moerloose; B Poppe; N Van Roy; K D Keersmaecker; J Cools; F Sigaux; J Soulier; A Hagemeijer; A D Paepe; N Dastugue; R Berger; F Speleman
• Keywords: Gene rearrangement

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.