Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Broyl A,Hose D,Lokhorst H,de Knegt Y,Peeters J,Jauch A,Bertsch U,Buijs A,Stevens-Kroef M,Beverloo HB,Vellenga E,Zweegman S,Kersten MJ,van der Holt B,el Jarari L,Mulligan G,Goldschmidt H,van Duin M,Sonneveld P

doi

10.1182/blood-2009-12-261032

subject

Has Abstract

pub_date

2010-10-07 00:00:00

pages

2543-53

issue

14

eissn

0006-4971

issn

1528-0020

pii

blood-2009-12-261032

journal_volume

116

pub_type

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