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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2020-2028.
Prepublished online as a Blood First Edition Paper on May 25, 2006; DOI 10.1182/blood-2005-11-013458.
 Previous Article | Next Article 
Submitted November 8, 2005
Accepted May 11, 2006
The molecular classification of multiple myeloma
Fenghuang Zhan, Yongsheng Huang, Simona Colla, James P Stewart, Ichiro Hanamura, Sushil Gupta, Joshua Epstein, Shmuel Yaccoby, Jeffrey Sawyer, Bart Burington, Klaus Hollmig, Mauricio Pineda-Roman, Guido Tricot, Frits van Rhee, Ronald Walker, Maurizio Zangari, John Crowley, Bart Barlogie, and John D Shaughnessy, Jr*
Donna D. & Donald M. Lambert Lab. of Myeloma Genetics, University of Arkansas for Medical Sciences
Myeloma Institute for Research & Therapy, University of Arkansas for Medical Sciences, AR, USA
Cancer Research and Biostatistics, Seattle, WA
* Corresponding author; email: shaughnessyjohn{at}uams.edu.
To better define the molecular basis of multiple myeloma
(MM) we performed unsupervised hierarchical clustering of
mRNA expression profiles from CD138-selected plasma cell
samples from 414 newly diagnosed patients who went on to
receive high dose therapy and tandem stem cell
transplants. Seven disease subtypes were validated that
were strongly influenced by known genetic lesions, such as
c-MAF- & MAFB-, CCND1- & CCND3- and
MMSET-activating translocations and hyperdiploidy.
Indicative of the deregulation of common pathways by gene
orthologs, common gene signatures were observed in cases
with c-MAF- and MAFB-activation and
CCND1- and CCND3-activation; the latter
consisting of two subgroups, one characterized by
expression of the early B-cell markers CD20 and
PAX5. A low incidence of focal bone disease
distinguished one and increased expression of
proliferation-associated genes another novel subgroup.
Comprising varying fractions of each of the other six
subgroups, the proliferation subgroup dominated at
relapse, suggesting that this signature is linked to
disease progression. Proliferation and MMSET-spike
groups were characterized by significant over-expression
of genes mapping to chromosome 1q and both exhibited a
poor prognosis relative to the other groups. A subset of
cases with a predominating myeloid gene expression
signature, excluded from the profiling analyses, had more
favorable baseline characteristics and superior prognosis
to those lacking this signature.
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112(4):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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[PDF]
|
|
|
|
|
|
|
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109(8):
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[Full Text]
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|
|
|
|
|
|
|
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67(7):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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March 15, 2007;
109(6):
2276 - 2284.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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6(3):
802 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. v. Rhee
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March 1, 2007;
13(5):
1353 - 1355.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dispenzieri, S. V. Rajkumar, M. A. Gertz, M. Q. Lacy, R. A. Kyle, P. R. Greipp, T. E. Witzig, J. A. Lust, S. J. Russell, S. R. Hayman, et al.
Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement
Mayo Clin. Proc.,
March 1, 2007;
82(3):
323 - 341.
[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]
|
|
|
|
|
|
|
S. Singhal and J. Mehta
Multiple Myeloma
Clin. J. Am. Soc. Nephrol.,
November 1, 2006;
1(6):
1322 - 1330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
