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

A. M. Aalbers, M. M. Van Den Heuvel-Eibrink, I. Baumann, H. B. Beverloo, G. J. Driessen, M. Dworzak, A. Fischer, G. Göhring, H. Hasle, F. Locatelli, B. De Moerloose, P. Noellke, M. Schmugge, J. Stary, A. Yoshimi, M. Zecca, C. M. Zwaan, J. J.M. Van Dongen, R. Pieters, C. M. NiemeyerV. H.J. Van Der Velden, A. W. Langerak

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8 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummere209
TijdschriftBlood Cancer Journal
Volume4
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - mei 2014
Extern gepubliceerdJa

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