6q- is an early and persistent chromosomal aberration in CD3-CD4+ T-cell clones associated with the lymphocytic variant of hypereosinophilic syndrome.
OBJECTIVE
The lymphocytic variant of hypereosinophilic syndrome (LV-HES) is an underrated disease defined by the monoclonal proliferation of interleukin-5 secreting T-cells. This disease is distinguished by a period of chronic lymphoproliferation without clinical transformation, which is frequently a precursor to T-cell lymphoma. In this study, LV-HES was used as a model of pre-malignancy to identify specific marker(s) predictive of the potential for malignant transformation.


METHODS
The karyotypic abnormalities detected in the abnormal CD3-CD4+ T cells were further characterized by fluorescent in situ hybridization. A multi-step retrospective analysis was performed on successive blood samples during a six-year follow up to correlate the evolution of cytogenetic changes with clinical progression. Expression array analysis was used to investigate the effect of these chromosomal aberrations on gene expression.


RESULTS
A 6q deletion was detected in the two LV-HES patients during their chronic disease phase. An additional 10p deletion was found alone or in association with the 6q defect in one patient prior to the development of a CD3-CD4+ T-cell lymphoma six years after diagnosis. We show that the 6q but not the 10p deletion is both stable and persistent throughout the chronic disease, finally emerging as the predominant aberration in the lymphoma cells. Six genes mapped to the 6q-deleted region displayed altered gene expression profiles both in the chronic and malignant disease phases.


CONCLUSIONS
Our data suggest that the 6q deletion represents an early cytogenetic marker for T-cell transformation.
Ravoet
Marie
M
Center for Human Genetics, Cliniques Universitaires St Luc UCL, Brussels, Belgium.
Sibille
Catherine
C
Roufosse
Florence
F
Duvillier
Hugues
H
Sotiriou
Christos
C
Schandené
Liliane
L
Martiat
Philippe
P
Goldman
Michel
M
Willard-Gallo
Karen E
KE
D000328:Adult; D001483:Base Sequence; D017252:CD3 Complex / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D002879:Chromosomes, Human, Pair 10; D002896:Chromosomes, Human, Pair 6; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000473:pathology; D008969:Molecular Sequence Data
D017252:CD3 Complex