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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4504-4511.
Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-01-0016.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis
Faith E. Davies,
Ann M. Dring,
Cheng Li,
Andrew C. Rawstron,
Masood A. Shammas,
Sheila M. O'Connor,
James A.L. Fenton,
Teru Hideshima,
Dharminder Chauhan,
Isabella T. Tai,
Elizabeth Robinson,
Daniel Auclair,
Karen Rees,
David Gonzalez,
A. John Ashcroft,
Ranjit Dasgupta,
Constantine Mitsiades,
Nicholas Mitsiades,
Lan B. Chen,
Wing H. Wong,
Nikhil C. Munshi,
Gareth J. Morgan, and
Kenneth C. Anderson
From the Academic Unit of Haematology and Oncology, University of Leeds, United Kingdom; Department of Biostatistics, Harvard School of Public Health, Boston; Department of Cancer Biology and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
To define specific pathways important in the multistep transformation process of normal plasma cells (PCs) to monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM), we have applied microarray analysis to PCs from 5 healthy donors (N), 7 patients with MGUS, and 24 patients with newly diagnosed MM. Unsupervised hierarchical clustering using 125 genes with a large variation across all samples defined 2 groups: N and MGUS/MM. Supervised analysis identified 263 genes differentially expressed between N and MGUS and 380 genes differentially expressed between N and MM, 197 of which were also differentially regulated between N and MGUS. Only 74 genes were differentially expressed between MGUS and MM samples, indicating that the differences between MGUS and MM are smaller than those between N and MM or N and MGUS. Differentially expressed genes included oncogenes/tumor-suppressor genes (LAF4, RB1, and disabled homolog 2), cell-signaling genes (RAS family members, B-cell signaling and NF- B genes), DNA-binding and transcription-factor genes (XBP1, zinc finger proteins, forkhead box, and ring finger proteins), and developmental genes (WNT and SHH pathways). Understanding the molecular pathogenesis of MM by gene expression profiling has demonstrated sequential genetic changes from N to malignant PCs and highlighted important pathways involved in the transformation of MGUS to MM. (Blood. 2003;102:4504-4511)
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