Molecular profiling of CD3(-)CD4(+) T cells from patients with the lymphocytic variant of hypereosinophilic syndrome reveals targeting of growth control pathways
(2009) Blood — Vol. 114, n° 14, p. 2969-2983 (2009)
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- Abstract
- 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 premalignant clone and the emergence of malignant sub-clones are unknown, precluding the development of targeted therapy for this HES variant. In this study, we used whole genome arrays 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 1 patient, with 87 of 349 genes representing further changes in genes whose expression was altered in all chronic disease patients (87 of 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 transforming growth factor-beta signaling, apoptosis, and T-cell maturation, signaling, and migration. Examination of microRNA expression in the CD3(-)CD4(+) T cells from patients with chronic disease identified 23 microRNAs that changed significantly, among which miR-125a further decreased in association with one patient's evolution to T lymphoma. (Blood. 2009; 114: 2969-2983)
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Ravoet, M., Sibille, C., Gu, C., Libin, M., Haibe-Kains, B., Sotiriou, C., Goldman, M., Roufosse, F., & Willard-Gallo, K. (2009). Molecular profiling of CD3(-)CD4(+) T cells from patients with the lymphocytic variant of hypereosinophilic syndrome reveals targeting of growth control pathways. Blood, 114(14), 2969-2983. https://doi.org/10.1182/blood-2008-08-175091 (Original work published 2009)