Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) b-chain variable (Vβ) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVβ skewing was present in 40% of RCC patients. TCRVβ skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVβ skewing was not clearly related with treatment response. However, TCRVβ skewing did correlate with a disturbed CD4+/CD8+ T-cell ratio, a reduction in naive CD8+ T cells, an expansion of effector CD8 + T cells and an increase in activated CD8+ T cells (defined as HLA-DR+, CD57+ or CD56+). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC. © 2014 Macmillan Publishers Limited. All rights reserved.
T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: A prospective study by EWOG-MDS / Aalbers, A. M.; Van Den Heuvel-Eibrink, M. M.; Baumann, I.; Beverloo, H. B.; Driessen, G. J.; Dworzak, M.; Fischer, A.; Gohring, G.; Hasle, H.; Locatelli, F.; De Moerloose, B.; Noellke, P.; Schmugge, M.; Stary, J.; Yoshimi, A.; Zecca, M.; Zwaan, C. M.; Van Dongen, J. J. M.; Pieters, R.; Niemeyer, C. M.; Van Der Velden, V. H. J.; Langerak, A. W.. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - 4:5(2014). [10.1038/bcj.2014.28]
T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: A prospective study by EWOG-MDS
Locatelli F.;
2014
Abstract
Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) b-chain variable (Vβ) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVβ skewing was present in 40% of RCC patients. TCRVβ skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVβ skewing was not clearly related with treatment response. However, TCRVβ skewing did correlate with a disturbed CD4+/CD8+ T-cell ratio, a reduction in naive CD8+ T cells, an expansion of effector CD8 + T cells and an increase in activated CD8+ T cells (defined as HLA-DR+, CD57+ or CD56+). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC. © 2014 Macmillan Publishers Limited. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
