Molecular profiling of
CD3-CD4+ T cells from patients with the lymphocytic variant of
hypereosinophilic syndrome reveals targeting of growth control pathways
Ravoet M, Sibille C, Gu C, Libin M, Haibe-Kains B, Sotiriou C, Goldman M, Roufosse F and Willard-Gallo K
The clonal CD3-CD4+ T-cell population characterizing lymphocytic
variant hypereosinophilic syndrome (L-HES) persists for years, with a
subgroup of patients ultimately progressing to T-lymphoma. The
molecular changes associated with the persistence of the pre-malignant
clone and the emergence of malignant subclones are unknown, precluding
the development of targeted therapy for this HES variant. In this
study, we used whole genome arrays, flow cytometry and qRT-PCR to
examine gene expression in the CD3-CD4+ T-cells and found that 850
genes were differentially regulated during chronic disease compared
with CD3+CD4+ T-cells from healthy donors. Changes in the expression of
349 genes were altered in association with the clinical progression
from chronic L-HES to T-lymphoma in one patient, with 87/349 genes
representing further changes in genes whose expression was altered in
all chronic disease patients (87/850). Array analysis after
CD2/CD28-mediated activation revealed that the major gene expression
changes observed in the CD3-CD4+ T-cells do not reflect activation
induced alterations but rather pathways involved in T-cell homeostasis,
including TGFβ signaling, apoptosis and T-cell maturation, signaling
and migration. MicroRNA expression in the CD3-CD4+ T-cells from
patients with chronic disease was examined using qRT-PCR and identified
23 microRNAs that changed significantly, among which miR-125a further
decreased in association with one patient’s evolution to T-lymphoma.