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.