Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia

Schuster FR, Hubner B, Führer M, Eckermann O, Gombert M, Dornmair K, Binder V, Reuther S, Krell P, Keller T, Borkhardt A (2011)
Blood Cancer Journal 1(3).

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Abstract
One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.
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Schuster FR, Hubner B, Führer M, et al. Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. Blood Cancer Journal. 2011;1(3).
Schuster, F. R., Hubner, B., Führer, M., Eckermann, O., Gombert, M., Dornmair, K., Binder, V., et al. (2011). Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. Blood Cancer Journal, 1(3).
Schuster, F. R., Hubner, B., Führer, M., Eckermann, O., Gombert, M., Dornmair, K., Binder, V., Reuther, S., Krell, P., Keller, T., et al. (2011). Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. Blood Cancer Journal 1.
Schuster, F.R., et al., 2011. Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. Blood Cancer Journal, 1(3).
F.R. Schuster, et al., “Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia”, Blood Cancer Journal, vol. 1, 2011.
Schuster, F.R., Hubner, B., Führer, M., Eckermann, O., Gombert, M., Dornmair, K., Binder, V., Reuther, S., Krell, P., Keller, T., Borkhardt, A.: Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. Blood Cancer Journal. 1, (2011).
Schuster, F R, Hubner, B, Führer, M, Eckermann, O, Gombert, M, Dornmair, K, Binder, V, Reuther, S, Krell, Pina, Keller, T, and Borkhardt, A. “Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia”. Blood Cancer Journal 1.3 (2011).
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2 Citations in Europe PMC

Data provided by Europe PubMed Central.

Quantitative T cell repertoire analysis by deep cDNA sequencing of T cell receptor α and β chains using next-generation sequencing (NGS).
Fang H, Yamaguchi R, Liu X, Daigo Y, Yew PY, Tanikawa C, Matsuda K, Imoto S, Miyano S, Nakamura Y., Oncoimmunology 3(12), 2014
PMID: 25964866
Next-generation-sequencing-spectratyping reveals public T-cell receptor repertoires in pediatric very severe aplastic anemia and identifies a β chain CDR3 sequence associated with hepatitis-induced pathogenesis.
Krell PF, Reuther S, Fischer U, Keller T, Weber S, Gombert M, Schuster FR, Asang C, Stepensky P, Strahm B, Meisel R, Stoye J, Borkhardt A., Haematologica 98(9), 2013
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