Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation

被引:95
作者
Soverini, S
Cavo, M
Cellini, C
Terragna, C
Zamagni, E
Ruggeri, D
Testoni, N
Tosi, P
de Vivo, A
Amabile, M
Grafone, T
Ottaviani, E
Giannini, B
Cangini, D
Bonifazi, F
Neri, A
Fabris, S
Tura, S
Baccarani, M
Martinelli, G
机构
[1] Univ Bologna, Inst Hematol & Med Oncol Seragnoli, I-40138 Bologna, Italy
[2] Osped Maggiore, IRCCS, Serv Ematol, Lab Ematol Sperimentale & Genet Mol, Milan, Italy
关键词
D O I
10.1182/blood-2002-12-3789
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We used a sensitive real-time reverse transcription-polymerase chain reaction assay to quantify cyclin D1 mRNA levels in bone marrow samples collected at diagnosis from 74 newly diagnosed multiple myeloma (MM) patients who were randomized to undergo either single or double autologous peripheral blood, stem cell transplantation as part of first-line therapy for their malignancy. In 46 cases, fluorescence in situ hybridization (FISH) analysis and/or conventional cytogenetics were performed to detect chromosome 11 abnormalities. Patients with the t(11;14) or trisomy 11 significantly overexpressed cyclin D1 (P <.0001) in comparison with patients without 11q abnormalities, who had cyclin Ell mRNA levels similar to healthy donors. Overall, 32 (43%) of 74 patients showed cyclin D1 overexpression. No difference was found between cyclin D1-positive (group A) and cyclin D1-negative (group B) patients with respect to presenting clinical and laboratory characteristics, including chromosome 13 abnormalities, as well as to response to therapy and overall survival, both of which were calculated on an intent-to-treat basis. Patients who overexpressed cyclin D1 had significantly longer duration of remission in comparison with patients who did not (41 vs 26 months, respectively; P =.02). As a result, median event-free survival (EFS) was longer in group A than in group B (33 vs 24 months, respectively; P =.055). We concluded that cyclin D1 overexpression is closely associated with 11q abnormalities and identifies a subset of MM patients who are more likely to have prolonged duration of remission and EFS following autologous transplantation.
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页码:1588 / 1594
页数:7
相关论文
共 35 条
[1]   Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation [J].
Avet-Loiseau, H ;
Facon, T ;
Grosbois, B ;
Magrangeas, F ;
Rapp, MJ ;
Harousseau, JL ;
Minvielle, S ;
Bataille, R .
BLOOD, 2002, 99 (06) :2185-2191
[2]  
Avet-Loiseau H, 1998, CANCER RES, V58, P5640
[3]   Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia:: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myelome and the Groupe Francais de Cytogenetique Hematologique [J].
Avet-Loiseau, H ;
Daviet, A ;
Brigaudeau, C ;
Callet-Bauchu, E ;
Terré, C ;
Lafage-Pochitaloff, M ;
Désangles, F ;
Ramond, S ;
Talmant, P ;
Bataille, R .
BLOOD, 2001, 97 (03) :822-825
[4]   Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma [J].
Bergsagel, PL ;
Chesi, M ;
Nardini, E ;
Brents, LA ;
Kirby, SL ;
Kuehl, WM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13931-13936
[5]  
Bergsagel PL, 1997, CURR TOP MICROBIOL, V224, P283
[6]  
Blade Joan, 1998, British Journal of Haematology, V102, P1115, DOI 10.1046/j.1365-2141.1998.00930.x
[7]   Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state [J].
Bounamici, S ;
Ottaviani, E ;
Testoni, N ;
Montefusco, V ;
Visani, G ;
Bonifazi, F ;
Amabile, M ;
Terragna, C ;
Ruggeri, D ;
Piccaluga, PP ;
Isidori, A ;
Malagola, M ;
Baccarani, M ;
Tura, S ;
Martinelli, G .
BLOOD, 2002, 99 (02) :443-449
[8]  
Cavo M, 2002, BLOOD, V100, p179A
[9]   Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines [J].
Chesi, M ;
Bergsagel, PL ;
Brents, LA ;
Smith, CM ;
Gerhard, DS ;
Kuehl, WM .
BLOOD, 1996, 88 (02) :674-681
[10]   The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts [J].
Chesi, M ;
Nardini, E ;
Lim, RSC ;
Smith, KD ;
Kuehl, WM ;
Bergsagel, PL .
BLOOD, 1998, 92 (09) :3025-3034