Publication: The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL) – the translocation defining a new T-ALL subtype in very young children.

Published in: Blood, 2007, Epub ahead of print. ⟨10.1182/blood-2006-12-064683⟩

Authors: Emmanuelle Clappier, Wendy Cuccuini, Anna Kalota, Antoine Crinquette, Jean-Michel Cayuela, Willem A Dik, Anton W Langerak, Bertrand Montpellier, Bertrand Nadel, Pierre Walrafen, Olivier Delattre, Alain Aurias, Thierry Leblanc, Herve Dombret, Alan M Gewirtz, Andre Baruchel, Francois Sigaux, Jean Soulier

Summary

The c-Myb transcription factor is essential for primitive and adult hematopoiesis, including in the T-cell lineage. The c-myb locus is a common site of retroviral insertional mutagenesis, however no recurrent genomic involvement has been reported in human malignancies. Here, we identified two types of genomic alterations involving the C-MYB locus at 6q23 in human T-cell acute leukemia (T-ALL). First, we found a reciprocal translocation, t(6;7)(q23;q34), that juxtaposed the TCRB and C-MYB loci (n=6 cases). Second, a genome wide copy-number analysis by array-CGH identified short somatic duplications which include C-MYB (MYB(dup), n=13 cases out of 84 T-ALL, 15%). Expression analysis, including allele-specific approaches, showed stronger C-MYB expression in the MYB-rearranged cases compared to other T-ALLs, and a dramatically skewed C-MYB allele expression in the TCRB-MYB cases which suggests that a translocation-driven deregulated expression may overcome a cellular attempt to downregulate C-MYB. Strikingly, profiling of the T-ALLs by clinical, genomic and large-scale gene expression analyses shows that the TCRB-MYB translocation defines a new T-ALL subtype associated with a very young age for T-cell leukemia (median 2.2 years-old) and with a proliferation/mitosis expression signature. By contrast, the MYB(dup) alteration was associated to the previously defined T-ALL subtypes.

Link to Pubmed [PMID] – 17452517

Link to HAL – hal-00165499

Link to DOI – 10.1182/blood-2006-12-064683