Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status - PubMed (original) (raw)

Multicenter Study

. 2006 Apr 1;107(7):2889-94.

doi: 10.1182/blood-2005-06-2227. Epub 2005 Nov 29.

Alexander Kröber, Fiona Murray, Ulf Thunberg, Gerard Tobin, Andreas Bühler, Dirk Kienle, Emilia Albesiano, Rossana Maffei, Lan-Phuong Dao-Ung, James Wiley, Juhani Vilpo, Anna Laurell, Mats Merup, Göran Roos, Karin Karlsson, Nicholas Chiorazzi, Roberto Marasca, Hartmut Döhner, Stephan Stilgenbauer, Richard Rosenquist

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Multicenter Study

Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status

Mia Thorsélius et al. Blood. 2006.

Free article

Abstract

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.

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