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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

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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 (Vb) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVb skewing was present in 40% of RCC patients. TCRVb 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, TCRVb skewing was not clearly related with treatment response. However, TCRVb 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.
Keywords
CYCLOSPORINE-A, POPULATION, CLINICAL-SIGNIFICANCE, IMMUNOSUPPRESSIVE THERAPY, AUTOLOGOUS LYMPHOCYTES, APLASTIC-ANEMIA, BONE-MARROW, ANTITHYMOCYTE GLOBULIN, RISK MYELODYSPLASTIC SYNDROME, PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA

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Citation

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Chicago
Aalbers, AM, MM van den Heuvel-Eibrink, I Baumann, HB Beverloo, GJ Driessen, M Dworzak, A Fischer, et al. 2014. “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.” Blood Cancer Journal 4.
APA
Aalbers, A., van den Heuvel-Eibrink, M., Baumann, I., Beverloo, H., Driessen, G., Dworzak, M., Fischer, A., et al. (2014). 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. BLOOD CANCER JOURNAL, 4.
Vancouver
1.
Aalbers A, van den Heuvel-Eibrink M, Baumann I, Beverloo H, Driessen G, Dworzak M, et al. 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. BLOOD CANCER JOURNAL. 2014;4.
MLA
Aalbers, AM et al. “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.” BLOOD CANCER JOURNAL 4 (2014): n. pag. Print.
@article{5867140,
  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 (Vb) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVb skewing was present in 40\% of RCC patients. TCRVb 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, TCRVb skewing was not clearly related with treatment response. However, TCRVb 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.},
  articleno    = {e209},
  author       = {Aalbers, AM and van den Heuvel-Eibrink, MM and Baumann, I and Beverloo, HB and Driessen, GJ and Dworzak, M and Fischer, A and G{\"o}hring, G and Hasle, H and Locatelli, F and De Moerloose, Barbara and Noellke, P and Schmugge, M and Stary, J and Yoshimi, A and Zecca, M and Zwaan, CM and van Dongen, JJM and Pieters, R and Niemeyer, CM and van der Velden, VHJ and Langerak, AW},
  issn         = {2044-5385},
  journal      = {BLOOD CANCER JOURNAL},
  language     = {eng},
  pages        = {7},
  title        = {T-cell receptor V\ensuremath{\beta} 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},
  url          = {http://dx.doi.org/10.1038/bcj.2014.28},
  volume       = {4},
  year         = {2014},
}

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