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Strikingly homologous immunoglobulin gene rearrangements and poor outcome inV(H)3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status
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2006 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 107, no 7, 2889-2894 p.Article in journal (Refereed) Published
Abstract [en]

We recently reported that Swedish V(H)3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite V-H mutation status. To investigate this further, we analyzed the V-H and V-L gene rearrangements in 90 V(H)3-21(+) 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 V-H genes and 37% unmutated V-H 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 V(lambda)2-14 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 V(H)3-21(+) CLILs have a remarkably predominant X expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the V(H)3-21(+) 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.

Place, publisher, year, edition, pages
2006. Vol. 107, no 7, 2889-2894 p.
National Category
Social Sciences
URN: urn:nbn:se:liu:diva-53493DOI: 10.1182/blood-2005-06-2227OAI: diva2:290020
Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2010-05-24

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