Konference: 2007 49th ASH Annual Meeting - účast ČR
Maligní lymfomy a leukémie
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,
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