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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 1925-1930
Deletion of 13q14 remains an independent adverse prognostic
variable in multiple myeloma despite its frequent detection by
interphase fluorescence in situ hybridization
Niklas Zojer,
Robert Königsberg,
Jutta Ackermann,
Elke Fritz,
Susanne Dallinger,
Elisabeth Krömer,
Hannes Kaufmann,
Lucia Riedl,
Heinz Gisslinger,
Susanne Schreiber,
Renate Heinz,
Heinz Ludwig,
Heinz Huber, and
Johannes Drach
From the Department of Internal Medicine I, Division of Clinical
Oncology, Division of Hematology and Hemostesiology, University of
Vienna; Department of Internal Medicine I with Medical Oncology,
Wilhelminenspital; Ludwig Boltzmann Institute for Leukemia
Research and Hematology; and the Third Department of Internal
Medicine, Hanuschspital, Vienna, Austria.
Interphase fluorescence in situ hybridization (FISH) studies of
chromosomal region 13q14 were performed to investigate the incidence
and clinical importance of deletions in multiple myeloma (MM).
Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the
D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of
72 (38.9%) patients, respectively, with newly diagnosed MM. FISH
studies found that 13q14 was deleted in all 17 patients with karyotypic
evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients
with apparently normal karyotypes. Patients with a 13q14 deletion were
more likely to have stage III disease (P = .022),
higher serum levels of  2-microglobulin (P = .059), and a higher percentage of bone marrow plasma cells
(P = .085) than patients with a normal 13q14 status on FISH
analysis. In patients with a deletion of 13q14, myeloma cell
proliferation (Ki-67) was markedly increased (22.0% ± 6.9% compared
with 15.6% ± 8.2% in patients without the deletion;
P = .0008). Evaluation of bromodeoxyuridine incorporation
in 5 patients revealed that both rb-1-deleted and rb-1-normal MM
subpopulations were proliferative. The presence of a 13q14 deletion on
FISH analysis was associated with a significantly lower rate of
response to conventional-dose chemotherapy (40.8% compared with
78.6%; P = .009) and a shorter overall survival (24.2 months compared with > 60 months; P < .005) than in
patients without the deletion. Multivariate analysis of prognostic
factors confirmed the independent predictive value of 13q14 deletions
for shortened survival. In conclusion, deletions of 13q14 are
frequently detected by interphase FISH in patients with newly diagnosed
MM, correlate with increased proliferative activity, and represent an
independent adverse prognostic feature in MM.
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