Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling.
Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P < 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-kappaB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients.
Chng
Wee J
WJ
Department of Hematology-Oncology, Mayo Clinic, Scottsdale, Arizona, USA. Chng.wee@mayo.edu
Kumar
Shaji
S
Vanwier
Scott
S
Ahmann
Greg
G
Price-Troska
Tammy
T
Henderson
Kim
K
Chung
Tae-Hoon
TH
Kim
Seungchan
S
Mulligan
George
G
Bryant
Barbara
B
Carpten
John
J
Gertz
Morie
M
Rajkumar
S Vincent
SV
Lacy
Martha
M
Dispenzieri
Angela
A
Kyle
Robert
R
Greipp
Philip
P
Bergsagel
P Leif
PL
Fonseca
Rafael
R
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D015331:Cohort Studies; D003907:Dexamethasone / Q000627:therapeutic use; D004171:Diploidy; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D005810:Multigene Family; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D014176:Protein Biosynthesis / Q000235:genetics; D011719:Pyrazines / Q000627:therapeutic use; D014314:Trisomy
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone