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

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 ( TCRβ ) (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 TCRβ-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 TCRβ-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b , was almost exclusively found in the TCRβ-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRβ-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 TCRβ-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRβ-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.