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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1737.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 1128-1140
NEOPLASIA
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 Jr
From the Donna and Donald Lambert Laboratory of Myeloma
Genetics at the Myeloma Institute for Research and Therapy, University
of Arkansas for Medical Sciences, Little Rock, AR.
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 (BCs) from 7 tonsils,
CD138-enriched PCs from 11 tonsils, 31 normal bone marrow samples, and
74 MM bone marrow samples using microarrays interrogating 6800 genes. Hierarchical clustering analyses with 3288 genes clearly
segregated the 4 cell types, and chi-square and Wilcoxin rank sum tests
(P < .0005) identified 359 and 500 previously defined
and novel genes that distinguish tonsil BCs from tonsil PCs (early
differentiation genes [EDGs]), and tonsil PCs from bone marrow PCs
(late differentiation genes [LDGs]), respectively. MM as a whole was
found to have dramatically variable expression of EDGs and
LDGs, and one-way analysis of variance (ANOVA) was used to identify the
most variable EDGs (vEDGs) and LDGs (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 3 normal cell types. Clustering with 30 vEDGs revealed that 13 of 18 MM4
cases clustered with tonsil BCs (P = .000 05), whereas
14 of 15 MM3 cases clustered with tonsil PCs when using 50 v1LDG
(P = .000 008), and 14 of 20 MM2 cases clustered with
bone marrow PCs when using 50 v2LDG
(P = .000 09). 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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