Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities.
Broyl
Annemiek
A
Department of Hematology, Erasmus Medical Center and University, Rotterdam, The Netherlands. a.broyl@erasmusmc.nl
Hose
Dirk
D
Lokhorst
Henk
H
de Knegt
Yvonne
Y
Peeters
Justine
J
Jauch
Anna
A
Bertsch
Uta
U
Buijs
Arjan
A
Stevens-Kroef
Marian
M
Beverloo
H Berna
HB
Vellenga
Edo
E
Zweegman
Sonja
S
Kersten
Marie-Josée
MJ
van der Holt
Bronno
B
el Jarari
Laila
L
Mulligan
George
G
Goldschmidt
Hartmut
H
van Duin
Mark
M
Sonneveld
Pieter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D016000:Cluster Analysis; D005060:Europe; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D010950:Plasma Cells / Q000378:metabolism*; D053668:Syndecan-1 / Q000378:metabolism; D055815:Young Adult
D053668:Syndecan-1