|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 March 2002, Vol. 99, No. 5, pp. 1745-1757
NEOPLASIA
Global gene expression profiling of multiple myeloma, monoclonal
gammopathy of undetermined significance, and normal bone marrow plasma
cells
Fenghuang Zhan,
Johanna Hardin,
Bob Kordsmeier,
Klaus Bumm,
Mingzhong Zheng,
Erming Tian,
Ralph Sanderson,
Yang Yang,
Carla Wilson,
Maurizio Zangari,
Elias Anaissie,
Christopher Morris,
Firas Muwalla,
Frits van Rhee,
Athanasios Fassas,
John Crowley,
Guido Tricot,
Bart Barlogie, and
John Shaughnessy Jr
From the Donna D. and Donald M. Lambert Laboratory of
Myeloma Genetics, Myeloma Institute for Research and Therapy, or
Department of Pathology, University of Arkansas for Medical Sciences,
Little Rock, and the Southwest Oncology Group, Fred Hutchinson Cancer
Research Center, Seattle, WA.
Bone marrow plasma cells (PCs) from 74 patients with newly
diagnosed multiple myeloma (MM), 5 with monoclonal gammopathy of undetermined significance (MGUS), and 31 healthy volunteers (normal PCs) were purified by CD138+ selection. Gene expression of
purified PCs and 7 MM cell lines were profiled using high-density
oligonucleotide microarrays interrogating about 6800 genes. On
hierarchical clustering analysis, normal and MM PCs were differentiated
and 4 distinct subgroups of MM (MM1, MM2, MM3, and MM4) were
identified. The expression pattern of MM1 was similar to normal PCs and
MGUS, whereas MM4 was similar to MM cell lines. Clinical parameters
linked to poor prognosis, abnormal karyotype (P = .002)
and high serum  2-microglobulin levels
(P = .0005), were most prevalent in MM4. Also, genes
involved in DNA metabolism and cell cycle control were overexpressed in a comparison of MM1 and MM4. In addition, using  2 and
Wilcoxon rank sum tests, 120 novel candidate disease genes were
identified that discriminate normal and malignant PCs
(P < .0001); many are involved in adhesion, apoptosis,
cell cycle, drug resistance, growth arrest, oncogenesis, signaling, and
transcription. A total of 156 genes, including FGFR3 and
CCND1, exhibited highly elevated ("spiked") expression
in at least 4 of the 74 MM cases (range, 4-25 spikes). Elevated
expression of these 2 genes was caused by the translocation
t(4;14)(p16;q32) or t(11;14)(q13;q32). Thus, novel candidate MM disease
genes have been identified using gene expression profiling and this
profiling has led to the development of a gene-based classification
system for MM.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y.-W. Qiang, J. D. Shaughnessy Jr, and S. Yaccoby
Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth
Blood,
July 15, 2008;
112(2):
374 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, A. Pennisi, and S. Yaccoby
Role of decorin in the antimyeloma effects of osteoblasts
Blood,
July 1, 2008;
112(1):
159 - 168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein
Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications
Clin. Cancer Res.,
December 15, 2007;
13(24):
7289 - 7295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Colla, S. Tagliaferri, F. Morandi, P. Lunghi, G. Donofrio, D. Martorana, C. Mancini, M. Lazzaretti, L. Mazzera, L. Ravanetti, et al.
The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 {alpha} (HIF-1{alpha}) activity: involvement in myeloma-induced angiogenesis
Blood,
December 15, 2007;
110(13):
4464 - 4475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Haessler, J. D. Shaughnessy Jr., F. Zhan, J. Crowley, J. Epstein, F. van Rhee, E. Anaissie, M. Pineda-Roman, M. Zangari, K. Hollmig, et al.
Benefit of Complete Response in Multiple Myeloma Limited to High-Risk Subgroup Identified by Gene Expression Profiling
Clin. Cancer Res.,
December 1, 2007;
13(23):
7073 - 7079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Stellrecht, C. J. Phillip, F. Cervantes-Gomez, and V. Gandhi
Multiple Myeloma Cell Killing by Depletion of the MET Receptor Tyrosine Kinase
Cancer Res.,
October 15, 2007;
67(20):
9913 - 9920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yang, V. MacLeod, Y. Dai, Y. Khotskaya-Sample, Z. Shriver, G. Venkataraman, R. Sasisekharan, A. Naggi, G. Torri, B. Casu, et al.
The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy
Blood,
September 15, 2007;
110(6):
2041 - 2048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zhan, S. Colla, X. Wu, B. Chen, J. P. Stewart, W. M. Kuehl, B. Barlogie, and J. D. Shaughnessy Jr
CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms
Blood,
June 1, 2007;
109(11):
4995 - 5001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L.M. Boylan, M. A. Gosse, S. E. Staggs, S. Janz, S. Grindle, G. S. Kansas, and B. G. Van Ness
A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma
Cancer Res.,
May 1, 2007;
67(9):
4069 - 4078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Hurt, S. B. Thomas, B. Peng, and W. L. Farrar
Integrated molecular profiling of SOD2 expression in multiple myeloma
Blood,
May 1, 2007;
109(9):
3953 - 3962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mulligan, C. Mitsiades, B. Bryant, F. Zhan, W. J. Chng, S. Roels, E. Koenig, A. Fergus, Y. Huang, P. Richardson, et al.
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
Blood,
April 15, 2007;
109(8):
3177 - 3188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Avet-Loiseau, M. Attal, P. Moreau, C. Charbonnel, F. Garban, C. Hulin, S. Leyvraz, M. Michallet, I. Yakoub-Agha, L. Garderet, et al.
Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome
Blood,
April 15, 2007;
109(8):
3489 - 3495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Standal, N. Abildgaard, U.-M. Fagerli, B. Stordal, O. Hjertner, M. Borset, and A. Sundan
HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma
Blood,
April 1, 2007;
109(7):
3024 - 3030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Shaughnessy Jr, F. Zhan, B. E. Burington, Y. Huang, S. Colla, I. Hanamura, J. P. Stewart, B. Kordsmeier, C. Randolph, D. R. Williams, et al.
A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
Blood,
March 15, 2007;
109(6):
2276 - 2284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Gold, K. R. Coombes, J. Wang, and B. Mallick
Enrichment analysis in high-throughput genomics--accounting for dependency in the NULL
Brief Bioinform,
March 1, 2007;
8(2):
71 - 77.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Cheng, M. H. L. Ng, K. M. Lau, H. S. Y. Liu, J. C. W. Chan, A. B. Y. Hui, K. W. Lo, H. Jiang, J. Hou, R. W. Chu, et al.
4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4
Blood,
March 1, 2007;
109(5):
2089 - 2099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yaccoby, W. Ling, F. Zhan, R. Walker, B. Barlogie, and J. D. Shaughnessy Jr
Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo
Blood,
March 1, 2007;
109(5):
2106 - 2111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zhan, B. Barlogie, V. Arzoumanian, Y. Huang, D. R. Williams, K. Hollmig, M. Pineda-Roman, G. Tricot, F. van Rhee, M. Zangari, et al.
Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis
Blood,
February 15, 2007;
109(4):
1692 - 1700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Agnelli, S. Bicciato, S. Fabris, L. Baldini, F. Morabito, D. Intini, D. Verdelli, A. Callegaro, F. Bertoni, G. Lambertenghi-Deliliers, et al.
Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma
Haematologica,
January 1, 2007;
92(1):
56 - 65.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Richardson, T. Hideshima, and K. C. Anderson
Plasma cell dyscrasias
ASH Self-Assessment Program,
January 1, 2007;
2007(1):
298 - 327.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Blade
Monoclonal Gammopathy of Undetermined Significance
N. Engl. J. Med.,
December 28, 2006;
355(26):
2765 - 2770.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Chng, R. F. Schop, T. Price-Troska, I. Ghobrial, N. Kay, D. F. Jelinek, M. A. Gertz, A. Dispenzieri, M. Lacy, R. A. Kyle, et al.
Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma
Blood,
October 15, 2006;
108(8):
2755 - 2763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zhan, Y. Huang, S. Colla, J. P. Stewart, I. Hanamura, S. Gupta, J. Epstein, S. Yaccoby, J. Sawyer, B. Burington, et al.
The molecular classification of multiple myeloma
Blood,
September 15, 2006;
108(6):
2020 - 2028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Hanamura, J. P. Stewart, Y. Huang, F. Zhan, M. Santra, J. R. Sawyer, K. Hollmig, M. Zangarri, M. Pineda-Roman, F. van Rhee, et al.
Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation
Blood,
September 1, 2006;
108(5):
1724 - 1732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bisping, M. Kropff, D. Wenning, B. Dreyer, S. Bessonov, F. Hilberg, G. J. Roth, G. Munzert, M. Stefanic, M. Stelljes, et al.
Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups
Blood,
March 1, 2006;
107(5):
2079 - 2089.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ely, M. Di Liberto, R. Niesvizky, L. B. Baughn, H. J. Cho, E. N. Hatada, D. M. Knowles, J. Lane, and S. Chen-Kiang
Mutually Exclusive Cyclin-Dependent Kinase 4/Cyclin D1 and Cyclin-Dependent Kinase 6/Cyclin D2 Pairing Inactivates Retinoblastoma Protein and Promotes Cell Cycle Dysregulation in Multiple Myeloma
Cancer Res.,
December 15, 2005;
65(24):
11345 - 11353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Dai, Y. Yang, V. MacLeod, X. Yue, A. C. Rapraeger, Z. Shriver, G. Venkataraman, R. Sasisekharan, and R. D. Sanderson
HSulf-1 and HSulf-2 Are Potent Inhibitors of Myeloma Tumor Growth in Vivo
J. Biol. Chem.,
December 2, 2005;
280(48):
40066 - 40073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. DHODAPKAR
Immune Response to Premalignancy: Insights from Patients with Monoclonal Gammopathy
Ann. N.Y. Acad. Sci.,
December 1, 2005;
1062(1):
22 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Boylan, M. A. Kvitrud, and B. G. Van Ness
A Trangenic Mouse Model of Plasma Cell Malignancy Shows Cytogenetic and Gene Expression Profiles Similar to Human Multiple Myeloma.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
619 - 619.
[Abstract]
|
|
|
|
|
|
|
S. A. Tomlins, D. R. Rhodes, S. Perner, S. M. Dhanasekaran, R. Mehra, X.-W. Sun, S. Varambally, X. Cao, J. Tchinda, R. Kuefer, et al.
Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer
Science,
October 28, 2005;
310(5748):
644 - 648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Agnelli, S. Bicciato, M. Mattioli, S. Fabris, D. Intini, D. Verdelli, L. Baldini, F. Morabito, V. Callea, L. Lombardi, et al.
Molecular Classification of Multiple Myeloma: A Distinct Transcriptional Profile Characterizes Patients Expressing CCND1 and Negative for 14q32 Translocations
J. Clin. Oncol.,
October 10, 2005;
23(29):
7296 - 7306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Chng, S. A. Van Wier, G. J. Ahmann, J. M. Winkler, S. M. Jalal, P. L. Bergsagel, M. Chesi, M. C. Trendle, M. M. Oken, E. Blood, et al.
A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS
Blood,
September 15, 2005;
106(6):
2156 - 2161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Stewart and R. Fonseca
Prognostic and Therapeutic Significance of Myeloma Genetics and Gene Expression Profiling
J. Clin. Oncol.,
September 10, 2005;
23(26):
6339 - 6344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. P. M. Tjin, R. J. Bende, P. W. B. Derksen, A.-P. van Huijstee, H. Kataoka, M. Spaargaren, and S. T. Pals
Follicular Dendritic Cells Catalyze Hepatocyte Growth Factor (HGF) Activation in the Germinal Center Microenvironment by Secreting the Serine Protease HGF Activator
J. Immunol.,
September 1, 2005;
175(5):
2807 - 2813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-W. Qiang, K. Walsh, L. Yao, N. Kedei, P. M. Blumberg, J. S. Rubin, J. Shaughnessy Jr, and S. Rudikoff
Wnts induce migration and invasion of myeloma plasma cells
Blood,
September 1, 2005;
106(5):
1786 - 1793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Girlanda, C. Fortis, D. Belloni, E. Ferrero, P. Ticozzi, C. Sciorati, M. Tresoldi, A. Vicari, T. Spies, V. Groh, et al.
MICA Expressed by Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Plasma Cells Costimulates Pamidronate-Activated {gamma}{delta} Lymphocytes
Cancer Res.,
August 15, 2005;
65(16):
7502 - 7508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Moreaux, F. W. Cremer, T. Reme, M. Raab, K. Mahtouk, P. Kaukel, V. Pantesco, J. De Vos, E. Jourdan, A. Jauch, et al.
The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature
Blood,
August 1, 2005;
106(3):
1021 - 1030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Bergsagel, W. M. Kuehl, F. Zhan, J. Sawyer, B. Barlogie, and J. Shaughnessy Jr
Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma
Blood,
July 1, 2005;
106(1):
296 - 303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Hodge, B. Peng, J. C. Cherry, E. M. Hurt, S. D. Fox, J. A. Kelley, D. J. Munroe, and W. L. Farrar
Interleukin 6 Supports the Maintenance of p53 Tumor Suppressor Gene Promoter Methylation
Cancer Res.,
June 1, 2005;
65(11):
4673 - 4682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
