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. Niemeyer & 2 others V. H J Van Der Velden, A. W. Langerak

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article numbere209
JournalBlood Cancer Journal
Volume4
Issue number5
DOIs
Publication statusPublished - 2014

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T-Cell Antigen Receptor
Prospective Studies
T-Lymphocytes
Immunosuppressive Agents
Bone Marrow
Therapeutics
Antilymphocyte Serum
Myelodysplastic Syndromes
Hematopoiesis
T-Lymphocyte Subsets
HLA-DR Antigens
Karyotype
Cyclosporine
Flow Cytometry
Clone Cells
History
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Medicine(all)

Cite this

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.; Göhring, 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, Vol. 4, No. 5, e209, 2014.

Research output: Contribution to journalArticle

Aalbers, AM, Van Den Heuvel-Eibrink, MM, Baumann, I, Beverloo, HB, Driessen, GJ, Dworzak, M, Fischer, A, Göhring, G, Hasle, H, Locatelli, F, De Moerloose, B, Noellke, P, Schmugge, M, Stary, J, Yoshimi, A, Zecca, M, Zwaan, CM, Van Dongen, JJM, Pieters, R, Niemeyer, CM, Van Der Velden, VHJ & Langerak, AW 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, vol. 4, no. 5, e209. https://doi.org/10.1038/bcj.2014.28
Aalbers, A. M. ; Van Den Heuvel-Eibrink, M. M. ; Baumann, I. ; Beverloo, H. B. ; Driessen, G. J. ; Dworzak, M. ; Fischer, A. ; Göhring, 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. / 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. In: Blood Cancer Journal. 2014 ; Vol. 4, No. 5.
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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 (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.",
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T1 - T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells

T2 - A prospective study by EWOG-MDS

AU - Aalbers, A. M.

AU - Van Den Heuvel-Eibrink, M. M.

AU - Baumann, I.

AU - Beverloo, H. B.

AU - Driessen, G. J.

AU - Dworzak, M.

AU - Fischer, A.

AU - Göhring, G.

AU - Hasle, H.

AU - Locatelli, F.

AU - De Moerloose, B.

AU - Noellke, P.

AU - Schmugge, M.

AU - Stary, J.

AU - Yoshimi, A.

AU - Zecca, M.

AU - Zwaan, C. M.

AU - Van Dongen, J. J M

AU - Pieters, R.

AU - Niemeyer, C. M.

AU - Van Der Velden, V. H J

AU - Langerak, A. W.

PY - 2014

Y1 - 2014

N2 - 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.

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