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Improved cytogenetics in multiple myeloma: a study of 151 patients
including 117 patients at diagnosis
JL Lai, M Zandecki, JY Mary, F Bernardi, V Izydorczyk, M Flactif, P Morel, JP Jouet, F Bauters and T Facon
Service de Cytogenetique and the Laboratoire d'Hematologie A, Hopital
Calmette, CHU, Lille, France.
Between December 1990 and January 1994, bone marrow (BM) samples from 151
patients with multiple myeloma (MM), including 117 patients evaluated at
diagnosis, were collected for cytogenetic analysis. A total of 129 patients
had assessable metaphases (100 patients at diagnosis). Cytogenetic studies
were performed on BM cells after longterm cultures (6 days) with
stimulation of cultures by granulocyte- macrophage colony-stimulating
factor (GM-CSF), GM-CSF plus interleukin (IL)-6, IL-3 plus IL-6, or GM-CSF
plus IL-3 plus IL-6 to improve myeloma cell growth, and 91 patients had an
additional unstimulated culture. Sixty-six patients (51%) had cytogenetic
abnormalities, including 47 of 100 patients at diagnosis (47%) and 17 of 24
patients at relapse (71%; P = .04). The aberration rate increased with
stage (P = .007), BM plasmacytosis (P = .003), beta 2 microglobulin level
(P = .001), C-reactive protein (CRP) level (P = .001), and Ki-67 (P =
.007). The abnormality detection rate was higher in stimulated than
unstimulated cultures, and the difference was statistically significant (P
< .01). Hyperdiploidy was observed in 39 patients (30% of patients with
an assessable karyotype) and hypodiploidy in 19 patients (15%). Among
numeric changes, gains predominantly involved chromosomes 3, 5, 7, 9, 11,
15, 19 and losses, chromosomes 8, 13, 14, and X. The most frequent loss was
loss of chromosome 13, observed in 22 patients (15%), including 18 patients
at diagnosis (12%). We observed frequent structural changes of chromosomes
1 (15%) and 14 (10%) but also a 5% incidence of 19q13 abnormality and two
patients with translocation t(1;16)(p11;p11). By using the proportional
hazard univariate model, patients with abnormal karyotypes were
demonstrated to have 2.5-fold greater chance of death than patients with
normal karyotypes (P < .014). Despite a multivariate approach with the
same model, the respective roles of karyotype abnormality, age, stage, and
beta 2 microglobulin level could not be clearly ascertained. From these
results we conclude that cytogenetic analysis using stimulation of cultures
by cytokine(s) may be a promising method to identify about 50% of
cytogenetic abnormalities in patients with newly diagnosed MM. Cytogenetic
analysis may help to define a high-risk population that would benefit from
intensive therapeutic approaches.
Volume 85,
Issue 9,
pp. 2490-2497,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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|
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|
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|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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November 1, 1998;
92(9):
3025 - 3034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Rao, J. C. Cigudosa, Y. Ning, M. J. Calasanz, S. Iida, S. Tagawa, J. Michaeli, B. Klein, R. Dalla-Favera, S. C. Jhanwar, et al.
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Blood,
September 1, 1998;
92(5):
1743 - 1748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Drach, J. Ackermann, E. Fritz, E. Kromer, R. Schuster, H. Gisslinger, M. DeSantis, N. Zojer, M. Fiegl, S. Roka, et al.
Presence of a p53 Gene Deletion in Patients With Multiple Myeloma Predicts for Short Survival After Conventional-Dose Chemotherapy
Blood,
August 1, 1998;
92(3):
802 - 809.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chesi, P. L. Bergsagel, O. O. Shonukan, M. L. Martelli, L. A. Brents, T. Chen, E. Schrock, T. Ried, and W. M. Kuehl
Frequent Dysregulation of the c-maf Proto-Oncogene at 16q23 by Translocation to an Ig Locus in Multiple Myeloma
Blood,
June 15, 1998;
91(12):
4457 - 4463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Cigudosa, P. H. Rao, M. J. Calasanz, M. D. Odero, J. Michaeli, S. C. Jhanwar, and R.S.K. Chaganti
Characterization of Nonrandom Chromosomal Gains and Losses in Multiple Myeloma by Comparative Genomic Hybridization
Blood,
April 15, 1998;
91(8):
3007 - 3010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hallek, P. Leif Bergsagel, and K. C. Anderson
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Blood,
January 1, 1998;
91(1):
3 - 21.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nishida, A. Tamura, N. Nakazawa, Y. Ueda, T. Abe, F. Matsuda, K. Kashima, and M. Taniwaki
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Blood,
July 15, 1997;
90(2):
526 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Bergsagel, M. Chesi, E. Nardini, L. A. Brents, S. L. Kirby, and W. M. Kuehl
Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma
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November 26, 1996;
93(24):
13931 - 13936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
