Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.
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.
Cauwelier
B
B
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Cavé
H
H
Gervais
C
C
Lessard
M
M
Barin
C
C
Perot
C
C
Van den Akker
J
J
Mugneret
F
F
Charrin
C
C
Pagès
M P
MP
Grégoire
M-J
MJ
Jonveaux
P
P
Lafage-Pochitaloff
M
M
Mozzicconacci
M J
MJ
Terré
C
C
Luquet
I
I
Cornillet-Lefebvre
P
P
Laurence
B
B
Plessis
G
G
Lefebvre
C
C
Leroux
D
D
Antoine-Poirel
H
H
Graux
C
C
Mauvieux
L
L
Heimann
P
P
Chalas
C
C
Clappier
E
E
Verhasselt
B
B
Benoit
Y
Y
Moerloose
B D
BD
Poppe
B
B
Van Roy
N
N
Keersmaecker
K D
KD
Cools
J
J
Sigaux
F
F
Soulier
J
J
Hagemeijer
A
A
Paepe
A D
AD
Dastugue
N
N
Berger
R
R
Speleman
F
F
D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015533:Transcriptional Activation; D014178:Translocation, Genetic
D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; C069634:HOXA10 protein, human