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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1737.
Submitted June 12, 2002
Accepted September 11, 2002
Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late stage B-cell development
Fenghuang Zhan, Erming Tian, Klaus Bumm, Ruston Smith, Bart Barlogie, and John Shaughnessy*
Myeloma and Transplantation Research Center, University of Arkansas for the Medical Sciences, Little Rock, AR, USA
Department of Otorhinolaryngology and Head and Neck Surgery, University of Erlangen-Nuremberg, Erlangen, Germany
* Corresponding author; email: shaughnessyjohn{at}exchange.uams.edu.
To identify genes linked to normal plasma cell (PC) differentiation and to classify multiple myeloma (MM) with respect to the expression patterns of these genes, we analyzed global mRNA expression in CD19-enriched B cells (BC) from 7 tonsils and CD138-enriched PC from 11 tonsils, 31 normal bone marrow and 74 MM bone marrow using microarrays interrogating 6,800 genes. Hierarchical clustering analyses with 3,288 genes clearly segregated the four cell types and Chi-square and Wilcoxin Rank sum tests (P < 0.0005) identified 359 and 500 previously defined and novel genes that distinguish tonsil BC from tonsil PC (early differentiation genes, EDG) and tonsil PC from bone marrow PC (late differentiation genes, LDG), respectively. MM as a whole was found to have dramatically variable expression of EDG and LDG and one-way ANOVA analysis was used to identify the most variable EDG (vEDG) and LDG (v1LDG and v2LDG). Hierarchical cluster analysis with these genes revealed that previously defined MM gene expression subgroups (MM1-MM4) could be linked to one of the three normal cell types. Clustering with 30 vEDG revealed that 13 of 18 MM4 clustered with tonsil BC (P = .00005), while 14 of 15 MM3 cases clustered with tonsil PC when using 50 v1LDG (P = .000008), and 14 of 20 MM2 cases clustered with bone marrow PC while clustering with 50 v2LDG (P=.00009). MM1 showed no significant linkage with normal cell types studied. Thus, genes whose expression is linked to distinct transitions in late stage B-cell differentiation can be used to classify MM.
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