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Hohe Strukturhomologie im Immunglobulin-Schwerketten-Rearrangement (IgVH) und ungünstiger Erkrankungsverlauf bei Patienten mit chronischer lymphatischer Leukämie (CLL) mit Umlagerung des VH3-21-Gens unabhängig von der geographischen Herkunft und dem VH-Mutationsstatus

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vts_6376_8582.pdf (609.0Kb)
105 Seiten
Veröffentlichung
2008-04-30
Authors
Bühler, Andreas
Dissertation


Faculties
Medizinische Fakultät
Abstract
We analyzed the VH and VL gene rearrangements in 90 VH3-21+ patients from Sweden, Germany, Italy, USA, Finland and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated VH genes and 37 % unmutated VH genes. Fifty patients (56 %) displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif, DANGMDV. Also, a highly biased Vl2-14 usage was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although VH3-21+ CLLs have a remarkably predominant l-expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the VH3-21+ cohort (median survival 88 months) with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21+ cases as well as a slight increase of 11q- aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21+ CLLs independent of geographical origin and mutation status.
Date created
2007
Subject headings
[GND]: Chronisch-lymphatische Leukämie
[MeSH]: Leukemia, lymphatic, chronic | Prognosis
[Free subject headings]: IgVH | IgVH-Rearrangement | Immunglobulin-Schwerketten-Rearrangement | VH3-21-Gen | VH-Mutationsstatus
[DDC subject group]: DDC 610 / Medicine & health
License
Standard (Fassung vom 03.05.2003)
https://oparu.uni-ulm.de/xmlui/license_v1

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-1397

Bühler, Andreas (2008): Hohe Strukturhomologie im Immunglobulin-Schwerketten-Rearrangement (IgVH) und ungünstiger Erkrankungsverlauf bei Patienten mit chronischer lymphatischer Leukämie (CLL) mit Umlagerung des VH3-21-Gens unabhängig von der geographischen Herkunft und dem VH-Mutationsstatus. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-1397
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