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11q deletions identify a new subset of B-cell chronic lymphocytic leukemia
characterized by extensive nodal involvement and inferior prognosis
H Dohner, S Stilgenbauer, MR James, A Benner, T Weilguni, M Bentz, K Fischer, W Hunstein and P Lichter
Medizinische Klinik and Poliklinik V, Universitat Heidelberg, Germany.
Deletions of the long arm of chromosome 11 (11q) are one of the most
frequent structural chromosome aberrations in various types of
lymphoproliferative disorders. However, in most conventional chromosome
banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q
deletions were not identified as a frequent aberration. The objective of
this study was to analyze the frequency and clinical impact of 11q
deletions in B-CLL by interphase cytogenetics using fluorescence in situ
hybridization (FISH). Mononuclear cells from 214 patients with B- CLL were
studied by FISH using the yeast artificial chromosome (YAC) clone 755b11
from chromosome region 11q22.3-q23.1; we previously showed that this clone
was contained within a 2- to 3-Mb sized segment of 11q commonly deleted in
lymphoproliferative disorders. Forty-three of the 214 (20%) tumors
exhibited 11q deletions; 11q deletions were the second most frequent
chromosome aberration following 13q14 (RB1 and/or D13S25) deletions (45%);
they were more frequent than trisomy 12 (15%) or deletion of 17p (TP53
gene) (10%). Patients with 11q deletions were younger (P = .01) and had
more advanced clinical stages (P = .01). 11q deletions were associated with
extensive peripheral, abdominal, and mediastinal lymphadenopathy (P <
.001). Patients with 11q deletions had a more rapid disease progression as
shown by a shorter treatment-free interval (9 months v 43 months; P <
.001). The prognostic effect of 11q deletion on survival strongly depended
on the age: in patients less than 55 years old, the median survival time
was significantly shorter in the deletion group (64 months v 209 months; P
< .001), whereas in patients > or = 55 years old there was no
significant difference (94 months v 111 months; P = .82). 11q deletions
identify a new clinical subset of B-CLL characterized by extensive lymph
node involvement. In younger B-CLL patients, this aberration is an
important predictor of survival.
Volume 89,
Issue 7,
pp. 2516-2522,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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