T-Cell Receptor V CDR3 Oligoclonality Frequently Occurs in Childhood Refractory Cytopenia and Severe Aplastic Anemia.

Konference: 2007 49th ASH Annual Meeting - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Postery

Číslo abstraktu: 2449

Autoři: C.H.Andrica de Vries ; Dr. Anton W. (Ton) Langerak ; Verhaaf Brenda; Prof. MD Charlotte M. Niemeyer, PhD; prof. MUDr. Jan Starý, DrSc.; Kjeld Schmiegelow; van Wering Elisabeth; Beishuizen Auke; Prof. MD Rob Pieters, PhD; MD Marry M. van den Heuvel-Eibrink, PhD

(Very) Severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow failure syndrome characterized by immune mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, in which the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality of TCR V CDR3 region, which is refered to as TCR V skewing. We investigated the value of TCR V repertoire analysis in pediatric MDS-RC and (v)SAA patients. Peripheral blood and/or bone marrow mononuclear samples of patients with (v)SAA (n=38), MDS-RC (n=28) and 18 controls were analysed with V heteroduplex analysis of extracted RNA. Skewing was found in 21/38 (55%) of the (v)SAA patients and in 17/28 (61%) of the RC patients. Seventeen patients with clinical (v)SAA showed no oligoclonality. A significant difference in TCR skewing was found between the (v)SAA + MDS-RC patients as compared to the controls (2 analysis, p=0.001), but not between MDS-RC and (v)SAA (2 analysis, p=0.8). In this study paired samples (PB and BM) of 25 cases showed a high correlation between the skewing results in both compartments (Pearson correlation, rr 0.98). In this study TCR V repertoire analysis did not discriminate between MDS-RC and (v)SAA. Prospective studies will be necessary to investigate whether there is a role for this molecular tool in pediatric MDS-RC for the identification of a subset of patients that is associated with auto-immunity and therfore could be treated with IST up-front, and whether it can be used for molecular response monitoring.

Abstract #2449 appears in Blood, Volume 110, issue 11, November 16, 2007

Keywords: Aplastic Anemia|MDS|T Cell Repertoire

Disclosure: No relevant conflicts of interest to declare.

Sunday, December 9, 2007 6:00 PM

Session Info: Poster Session: Myelodysplastic Syndromes: Molecular Biology and Pathogenesis (6:00 p.m.-8:00 p.m.)

Datum přednesení příspěvku: 9. 12. 2007