Biological and clinical characterization of recurrent 14q deletions in CLL and other mature B-cell neoplasms.

Abstract

14q-deletions have been repeatedly described in mature B-cell neoplasms, but not yet characterized in a larger cohort. Based on chromosome banding analysis, the present study identified 47 del(14q) cases in 3054 mature B-cell neoplasms (1·5%) (chronic lymphocytic leukaemia [CLL]: 1·9%; CLL/prolymphocytic leukaemia [PL]: 9·0%; others: 0·2%). Interphase fluorescence in situ hybridization was performed with probes for 14q22.1, 14q24.1, 14q32.33, and IGH@ (14q32.3). The del(14q) had heterogeneous size but showed a breakpoint cluster at the centromeric site in 14q24.1 (62% of cases). At the telomeric side, the most frequent breakpoint was within the IGH@ locus (14q32.3) between IGH@ 3'-flanking and IGHV (IgVH) probes (45%). In 16 cases (34%), breakpoints occurred within 14q24.1 and 14q32.3. Eighty-one percent of del(14q) cases showed 1-3 additional cytogenetic alterations (in 45%, +12), and 56% were IGHV-unmutated. In all cases (16/16) with breakpoints in 14q24.1 and 14q32.3, a B-CLL immunophenotype was found. Clinical follow-up in 32 del(14q) patients was compared to 383 CLL and CLL/PL patients without del(14q). While 3-year-overall survival did not differ significantly, time to treatment was significantly shorter in the del(14q) cohort (21·0 months vs. 80·1 months, P = 0·015). In conclusion, the del(14q) is a rare recurrent alteration in diverse mature B-cell neoplasms, shows variable size but distinct clustering of breakpoints, and is associated with short time to treatment.

• Authors: Lena Reindl, Ulrike Bacher, Frank Dicker, Tamara Alpermann, Wolfgang Kern, Susanne Schnittger, Torsten Haferlach, Claudia Haferlach
• Journal: British journal of haematology (Br J Haematol) Vol. 151 Issue 1 Pg. 25-36 (Oct 2010) ISSN: 1365-2141 [Electronic] England
• PMID: 20649559 (Publication Type: Journal Article)
• Copyright: © 2010 Blackwell Publishing Ltd.

Chemical References

• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region

Topics

• Aged
• Aged, 80 and over
• Chromosome Aberrations
• Chromosome Deletion
• Chromosomes, Human, Pair 14 (genetics)
• Female
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• In Situ Hybridization, Fluorescence
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics)
• Leukemia, Prolymphocytic (genetics)
• Male
• Middle Aged
• Mutation
• Prognosis
• Survival Analysis