- Blood. 2006 Apr
1;107(7):2889-94. Epub 2005 Nov 29.
Strikingly homologous immunoglobulin gene rearrangements and
poor outcome in VH3-21-using chronic lymphocytic leukemia
patients independent of geographic origin and mutational
status.
Thorselius M, Krober A, Murray F, Thunberg U, Tobin G,
Buhler A, Kienle D, Albesiano E, Maffei R, Dao-Ung LP, Wiley
J, Vilpo J, Laurell A, Merup M, Roos G, Karlsson K,
Chiorazzi N, Marasca R, Dohner H, Stilgenbauer S, Rosenquist
R.
Department of Genetic and Pathology, Rudbeck Laboratory,
Uppsala University, SE-751 85 Uppsala, Sweden.
We recently reported that Swedish VH3-21-using chronic
lymphocytic leukemia (CLL) patients showed restricted
immunoglobulin gene features and poor prognosis despite VH
mutation status. To investigate this further, we analyzed
the VH and VL gene rearrangements in 90 VH3-21+ patients
from Sweden, Germany, Italy, United States, 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 (56%) patients
displayed a short and homologous heavy-chain CDR3, many of
these with the amino acid motif DANGMDV. Also, a highly
biased Vlambda2-14 use 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 lambda 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 geographic origin and mutation status.
PMID: 16317103 [PubMed - indexed for MEDLINE]
|