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

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.