NPM1 is overexpressed in hyperdiploid multiple myeloma due to a gain of chromosome 5 but is not delocalized to the cytoplasm.
Multiple myeloma (MM) is proposed to consist of two main pathogenetic groups. Although hyperdiploid MM (HD) is characterized by multiple trisomies of odd chromosomes, in nonhyperdiploid MM (NHD), one of the recurrent primary immunoglobulin heavy chain (IGH) translocations and deletion of chromosome 13 can frequently be found. In this study, we analyzed gene-expression profiles of patients with previously untreated MM. Fifty-four genes were significantly differentially expressed between the two groups. NPM1 was upregulated in HD. The differential expression of 25 genes, including NPM1 and 13 ribosomal protein genes, was validated using a published gene expression data set. The overexpression of NPM1 in HD was further confirmed by quantitative real-time PCR and Western blotting. NPM1 was significantly overexpressed in HD as the result of a gain of chromosome 5. Insertions into exon 12 of NPM1 were not detected. NPM1 was localized to the nucleoli of MM cells. Furthermore, HD was associated with an overexpression of ribosomal protein genes, independent of their localization on the trisomic or other chromosomes. Our results indicate that the gain of chromosome 5 might play an important role in the pathogenesis of HD.
Weinhold
Niels
N
Medizinische Klinik V, Universitaetsklinikum Heidelberg, Heidelberg, Germany.
Moreaux
Jerome
J
Raab
Marc S
MS
Hose
Dirk
D
Hielscher
Thomas
T
Benner
Axel
A
Meissner
Tobias
T
Ehrbrecht
Edith
E
Brough
Michaela
M
Jauch
Anna
A
Goldschmidt
Hartmut
H
Klein
Bernard
B
Moos
Marion
M
D000782:Aneuploidy; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D015854:Up-Regulation
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012269:Ribosomal Proteins; D000090243:Nucleophosmin