Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.
Barbara Cauwelier
(1)
,
Hélène Cavé
(2)
,
Carine Gervais
(3)
,
Michel Lessard
(3)
,
Carole Barin
(4)
,
Christine Perot
(5)
,
Jacqueline van den Akker
(5)
,
Francine Mugneret
(6)
,
Christiane Charrin
(7)
,
Marie Pierre Pagès
(7)
,
Marie-José Grégoire
(8)
,
Philippe Jonveaux
(8)
,
Marina Lafage-Pochitaloff
(9)
,
Marie Joelle Mozzicconacci
(9)
,
Christine Terré
(10)
,
Isabelle Luquet
(11)
,
Pascale Cornillet-Lefebvre
(11)
,
Bernard Laurence
(12)
,
Ghislaine Plessis
(13)
,
Christine Lefebvre
(14)
,
Dominique Leroux
(14)
,
Hélène Antoine-Poirel
(15)
,
Carlos Graux
(16)
,
Laurent Mauvieux
(3)
,
Pierre Heimann
(17)
,
Céline Chalas
(2)
,
Emmanuel Clappier
(4)
,
Bruno Verhasselt
(18)
,
Yves Benoit
(19)
,
Barbara Moerloose
(19)
,
Bruce Poppe
(1)
,
Nadine van Roy
(1)
,
Kim De Keersmaecker
(20)
,
Jan Cools
(20)
,
François Sigaux
(16)
,
Roland Berger
(21)
,
Jean Soulier
(16)
,
Anne Hagemeijer
(22)
,
Anne Paepe
(1)
,
Nicole Dastugue
(23)
,
Franck Speleman
(1)
1
Center for Medical Genetics [Ghent]
2 Laboratoire de Biochimie Génétique
3 Laboratoire d'Hématologie
4 CHU Bretonneau
5 UMRS893 - Centre de Recherche Saint-Antoine
6 CHU Dijon
7 Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL]
8 Service de Génétique [CHRU Nancy]
9 IPC - Institut Paoli-Calmettes
10 CHV - Centre Hospitalier de Versailles André Mignot
11 Hôpital Maison Blanche
12 Hôpital Robert Debré
13 Service de Génétique [CHU Caen]
14 Bases moléculaires de la progression tumorale -Groupe de Recherche sur les Lymphomes
15 Centre for Medical genetics
16 Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique
17 Department of Medical Genetics
18 Centre for Molecular Diagnostics
19 Department of Pediatric Hematology/Oncology
20 Department of Human Genetics
21 Hôpital Necker - Enfants Malades [AP-HP]
22 Centre for Human Genetics
23 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
2 Laboratoire de Biochimie Génétique
3 Laboratoire d'Hématologie
4 CHU Bretonneau
5 UMRS893 - Centre de Recherche Saint-Antoine
6 CHU Dijon
7 Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL]
8 Service de Génétique [CHRU Nancy]
9 IPC - Institut Paoli-Calmettes
10 CHV - Centre Hospitalier de Versailles André Mignot
11 Hôpital Maison Blanche
12 Hôpital Robert Debré
13 Service de Génétique [CHU Caen]
14 Bases moléculaires de la progression tumorale -Groupe de Recherche sur les Lymphomes
15 Centre for Medical genetics
16 Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique
17 Department of Medical Genetics
18 Centre for Molecular Diagnostics
19 Department of Pediatric Hematology/Oncology
20 Department of Human Genetics
21 Hôpital Necker - Enfants Malades [AP-HP]
22 Centre for Human Genetics
23 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
Laurent Mauvieux
- Fonction : Auteur
- PersonId : 760697
- ORCID : 0000-0002-9043-1845
- IdRef : 067407463
Franck Speleman
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- Fonction : Auteur correspondant
- PersonId : 856776
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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 (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.