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, F. R.; Hubner, B.; Fuehrer, M.; Eckermann, O.; Gombert, M.; Dornmair, Klaus; Binder, V.; Reuther, S.; Krell, P.; Keller, T.; Borkhardt, A.

doi:10.1038/bcj.2011.6

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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

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Dornmair, Klaus
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Citation

Schuster, F. R., Hubner, B., Fuehrer, M., Eckermann, O., Gombert, M., Dornmair, K., 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: e8. doi:10.1038/bcj.2011.6.

Cite as: https://hdl.handle.net/11858/00-001M-0000-000F-3D49-C

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. Blood Cancer Journal (2011) 1, e8;
doi:10.1038/bcj.2011.6; published online 4 March 2011