Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCR beta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique
Fiche publication
Date publication
janvier 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CORNILLET-LEFEBVRE Pascale, Pr MAUVIEUX Laurent
Tous les auteurs :
Cauwelier B, Cave H, Gervais C, Lessard M, Barin C, Perot C, Van den Akker J, Mugneret F, Charrin C, Pages MP, Gregoire MJ, Jonveaux P, Lafage-Pochitaloff M, Mozzicconacci MJ, Terre C, Luquet I, Cornillet-Lefebvre P, Laurence B, Plessis G, Lefebvre C, Leroux D, Antoine-Poirel H, Graux C, Mauvieux L, Heimann P, Chalas C, Clappier E, Verhasselt B, Benoit Y, Moerloose BD, Poppe B, Van Roy N, Keersmaecker KD, Cools J, Sigaux F, Soulier J, Hagemeijer A, Paepe AD, Dastugue N, Berger R, Speleman F
Lien Pubmed
Résumé
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 ( TCR beta) ( 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 TCR beta-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 TCR beta-HOXA rearrangement ( 8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCR beta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCR beta-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 TCRb- HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCR beta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
Référence
Leukemia. 2007 Jan;21(1):121-8